Aspiration catheter systems and methods of use

ABSTRACT

Described are methods, systems, devices for facilitation of intraluminal medical procedures within the neurovasculature. A catheter advancement device includes a flexible elongate body having a proximal end, a distal end, and a single lumen extending therebetween. The flexible elongate body has a proximal segment, an intermediate segment, and a tip segment. The proximal segment includes a hypotube coated with a polymer. The intermediate segment includes an unreinforced polymer having a durometer of no more than 72 D. The tip segment is formed of a polymer different from the intermediate segment and has a durometer of no more than about 35 D and a length of at least 5 cm. The tip segment has a tapered portion that tapers distally from a first outer diameter to a second outer diameter over a length of between 1 and 3 cm.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is continuation-in-part of co-pending U.S. patentapplication Ser. No. 15/866,012, filed on Jan. 9, 2018, which claims thebenefit of priority under 35 U.S.C. § 119(e) to U.S. Provisional PatentApplication Ser. No. 62/444,584, filed Jan. 10, 2017, and 62/607,510,filed Dec. 19, 2017.

This application is also a continuation-in-part of co-pending U.S.patent application Ser. No. 15/727,373 filed Oct. 6, 2017, which is acontinuation of U.S. application Ser. No. 15/217,810, filed Jul. 22,2016, now U.S. Pat. No. 10,426,497, issued Oct. 1, 2019, which claimsthe benefit of priority to U.S. Provisional Application Nos. 62/196,613,filed Jul. 24, 2015, and 62/275,939, filed Jan. 7, 2016, and 62/301,857,filed Mar. 1, 2016.

This application is also a continuation-in-part of co-pending U.S.patent application Ser. No. 16/584,351, filed Sep. 26, 2019, which is acontinuation of U.S. patent application Ser. No. 15/875,214, filed Jan.19, 2018, which claims the benefit of priority under 35 U.S.C. § 119(e)to U.S. Provisional Patent Application Ser. Nos. 62/448,678, filed Jan.20, 2017, and 62/517,005, filed Jun. 8, 2017.

This application is also a continuation-in-part of co-pending U.S.patent application Ser. No. 16/543,215, filed Aug. 16, 2019, which iscontinuation of U.S. patent application Ser. No. 15/856,979, filed Dec.28, 2017, now U.S. Pat. No. 10,456,555, issued Oct. 29, 2019, which is acontinuation of U.S. application Ser. No. 15/805,673, filed Nov. 7,2017, now U.S. Pat. No. 10,485,952, issued Nov. 26, 2019, which is acontinuation of U.S. patent application Ser. No. 15/015,799, filed Feb.4, 2016, now U.S. Pat. No. 9,820,761, issued Nov. 21, 2017, which claimspriority to U.S. Provisional Application Ser. No. 62/111,481, filed Feb.4, 2015, and U.S. Provisional Application Ser. No. 62/142,637, filedApr. 3, 2015.

The disclosures are each incorporated by reference in their entireties.

FIELD

The present technology relates generally to medical devices and methods,and more particularly, to aspiration catheter systems and their methodsof use.

BACKGROUND

Acute ischemic stroke (AIS) usually occurs when an artery to the brainis occluded, preventing delivery of fresh oxygenated blood from theheart and lungs to the brain. These occlusions are typically caused by athrombus or an embolus lodging in the artery and blocking the arterythat feeds a territory of brain tissue. If an artery is blocked,ischemia injury follows, and brain cells may stop working. Furthermore,if the artery remains blocked for more than a few minutes, the braincells may die, leading to permanent neurological deficit or death.Therefore, immediate treatment is critical.

Two principal therapies are employed for treating ischemic stroke:thrombolytic therapy and endovascular treatment. The most commontreatment used to reestablish flow or re-perfuse the stroke territory isthe use of intravenous (IV) thrombolytic therapy. The timeframe to enactthrombolytic therapy is within 3 hours of symptom onset for IV infusion(4.5 hours in selected patients) or within 6 hours for site-directedintra-arterial infusion. Instituting therapy at later times has noproven benefit and may expose the patient to greater risk of bleedingdue to the thrombolytic effect. Endovascular treatment most commonlyuses a set of tools to mechanically remove the embolus, with our withoutthe use of thrombolytic therapy.

The gamut of endovascular treatments include mechanical embolectomy,which utilizes a retrievable structure, e.g., a coil-tipped retrievablestent (also known as a “stent retriever” or a STENTRIEVER), a woven wirestent, or a laser cut stent with struts that can be opened within a clotin the cerebral anatomy to engage the clot with the stent struts, createa channel in the emboli to restore a certain amount of blood flow, andto subsequently retrieve the retrievable structure by pulling it out ofthe anatomy, along with aspiration techniques. Other endovasculartechniques to mechanically remove AIS-associated embolus include ManualAspiration Thrombectomy (MAT) (also known as the “ADAPT” technique).ADAPT/MAT is an endovascular procedure where large bore catheters areinserted through the transfemoral artery and maneuvered through complexanatomy to the level of the embolus, which may be in the extracranialcarotids, vertebral arteries, or intracranial arteries. Aspirationtechniques may be used to remove the embolus through the large borecatheters. Another endovascular procedure is Stentriever-Mediated ManualAspiration Thrombectomy (SMAT) (similar to the Stentriever-assisted“Solumbra” technique). SMAT, like MAT, involves accessing the embolusthrough the transfemoral artery. After access is achieved, however, aretrievable structure is utilized to pull the embolus back into a largebore catheter.

To access the cerebral anatomy, guide catheters or guide sheaths areused to guide interventional devices to the target anatomy from anarterial access site, typically the femoral artery. The length of theguide is determined by the distance between the access site and thedesired location of the guide distal tip. Interventional devices such asguidewires, microcatheters, and intermediate catheters used forsub-selective guides and aspiration, are inserted through the guide andadvanced to the target site. Often, devices are used in a co-axialfashion, namely, a guidewire inside a microcatheter inside anintermediate catheter is advanced as an assembly to the target site in astepwise fashion with the inner, most atraumatic elements, advancingdistally first and providing support for advancement of the outerelements. The length of each element of the coaxial assemblage takesinto account the length of the guide, the length of proximal connectorson the catheters, and the length needed to extend from the distal end.

Typical tri-axial systems such as for aspiration or delivery of stentretrievers and other interventional devices require overlapped series ofcatheters, each with their own rotating hemostatic valves (RHV) on theproximal end. For example, a guidewire can be inserted through aPenumbra Velocity microcatheter having a first proximal RHV, which canbe inserted through a Penumbra ACE68 having a second proximal RHV, whichcan be inserted through a Penumbra NeuronMAX 088 access catheter havinga third proximal RHV positioned in the high carotid via a femoralintroducer. Maintaining the coaxial relationships between thesecatheters can be technically challenging. The three RHVs must beconstantly adjusted with two hands or, more commonly, four hands (i.e.two operators). Further, the working area of typical tri-axial systemsfor aspiration and/or intracranial device delivery can require workingarea of 3-5 feet at the base of the operating table.

The time required to access the site of the occlusion and restore, evenpartially, flow to the vessel is crucial in determining a successfuloutcome of such procedures. Similarly, the occurrence of distal emboliduring the procedure and the potentially negative neurologic effect andprocedural complications such as perforation and intracerebralhemorrhage are limits to success of the procedure. There is a need for asystem of devices and methods that allow for rapid access, optimizedcatheter aspiration, and treatment to fully restore flow to the blockedcerebral vessel.

SUMMARY

In an aspect, described is an intravascular catheter advancement devicefor advancing a catheter within the neurovasculature. The catheteradvancement device includes a flexible elongate body having a proximalend, a distal end, and a single lumen extending therebetween. Theflexible elongate body includes a proximal segment having a hypotubecoated with a polymer; an intermediate segment having an unreinforcedpolymer having a durometer of no more than 72 D; and a tip segment. Thetip segment is formed of a polymer different from the intermediatesegment and has a durometer of no more than about 35 D and a length ofat least 5 cm. The tip segment has a tapered portion which tapersdistally from a first outer diameter to a second outer diameter over alength of between 1 and 3 cm. The catheter advancement device has alength configured to extend from outside the patient's body, through thefemoral artery, and to the petrous portion of the internal carotidartery and an inner diameter less than 0.024 inches to accommodate aguidewire.

The flexible elongate body can be formed without a tubular inner liner.The unreinforced polymer of the flexible elongate body can incorporate alubricious additive. A taper angle of the wall of the tapered portionrelative to a center line of the tapered portion can be between 0.9 to1.6 degrees (or 2-3 degrees). The second outer diameter can be about ½of the first outer diameter. The second outer diameter can be about 40%of the first outer diameter. The second outer diameter can be about 65%of the first outer diameter. The intermediate segment can include afirst segment having a material hardness of no more than 55 D and asecond segment located proximal to the first segment having a materialhardness of no more than 72 D.

The catheter advancement device can be part of a system including acatheter having a lumen and a distal end. An outer diameter of theflexible elongate body can be sized to be positioned coaxially withinthe catheter lumen such that the tapered portion of the tip segmentextends distally beyond the distal end of the catheter to aid indelivery of the catheter to an intracranial vessel.

The flexible elongate body can have an insert length that is at leastabout 49 cm. A location of a material transition between theunreinforced polymer and the hypotube can be at least about 49 cm fromthe distal end of the flexible elongate body. The location can allow forpositioning the material transition proximal to the brachiocephalictake-off in the aortic arch when the distal end is positioned within thepetrous portion of the internal carotid artery. The hypotube can have aninner diameter of about 0.021″ and an outer diameter of about 0.027″.The first outer diameter can be about 0.062″ up to about 0.080″. Thesecond outer diameter can be about 0.031″. The tip segment can include afirst radiopaque marker and a second radiopaque marker. The firstradiopaque marker can be positioned on the first outer diameter andidentify a border between the first outer diameter and the taperedportion. The second radiopaque marker can be positioned on the secondouter diameter. The first and second radiopaque markers can havedifferent widths. The first and second radiopaque markers can beextruded polymer loaded with a radiopaque material, the radiopaquematerial being platinum/iridium, tungsten, or tantalum.

The catheter advancement device can be configured for insertion over theguidewire such that the guidewire extends through the single lumen fromthe proximal end to the distal end. The proximal end can have a proximalopening and the distal end can have a distal opening, the proximal anddistal openings sized to receive the guidewire. The catheter advancementdevice can further include a rapid exchange opening through a wall. Thehypotube can be coated with a lubricious polymer. The lubricious polymercan be PTFE. The hypotube can be circular, oval, or trapezoidal D shapein cross-section. The hypotube can be a skived hypotube of stainlesssteel. The skived hypotube can be coupled to a proximal hub. Theproximal hub can include a luer thread and a luer taper inside of thehub. The proximal hub can prevent insertion of the proximal hub througha proximal RHV.

In an aspect, described is an intravascular catheter advancement devicefor facilitation of intraluminal medical procedures within theneurovasculature. The catheter advancement device includes a flexibleelongate body having a proximal end region, an outer diameter, a tapereddistal tip portion, a distal opening, and a single lumen extendinglongitudinally through the flexible elongate body to the distal opening;and a proximal portion coupled to the proximal end region of theflexible elongate body. The proximal portion extends proximally to aproximal-most end of the catheter advancement element. A hardness of theflexible elongate body transitions proximally towards increasinglyharder materials up to the proximal portion forming a first plurality ofmaterial transitions. At least a portion of the flexible elongate bodyis formed of a plurality of layers including a reinforcement layer. Theouter diameter of the flexible elongate body is sized to be positionedcoaxially within a lumen of a catheter such that the distal tip portionof the flexible elongate body extends distally beyond a distal end ofthe catheter to aid in delivery of the catheter to an intracranialvessel.

The reinforcement layer can be a braid. The braid can extend from theproximal end region of the flexible elongate body and terminate at apoint proximal to the distal tip portion. The point can be locatedbetween 4 cm and 15 cm from a distal-most terminus of the flexibleelongate body. The plurality of layers can further include a firstpolymer material layer and a second polymer material layer. The braidcan be positioned between the first and second polymer material layers.The proximal portion can be a hypotube having a distal end coupled tothe flexible elongate body. The braid can be positioned between thefirst and second polymer material layers and positioned over the distalend of the hypotube.

The distal tip portion can include a material having a material hardnessthat is no more than 35 D. The proximal end region of the elongate bodycan include a material having a material hardness that is between 55 Dto 72 D. The elongate body can include a first segment including thedistal tip portion having a hardness of no more than 35 D. The elongatebody can include a second segment located proximal to the first segmenthaving a hardness of no more than 55 D. The elongate body can include athird segment located proximal to the second segment having a hardnessof no more than 72 D. The proximal portion can couple to the elongatebody within the third segment. The first segment can be unreinforced andthe third segment can be reinforced. The second segment can be at leastpartially reinforced. A reinforcement braid can extend through at leastthe third segment. The first, second, and third segments can combine toform an insert length of the elongate body. The first segment can have alength of about 4 cm to about 12.5 cm. The second segment can have alength of about 5 cm to about 8 cm. The third segment can have a lengthof about 25 cm to about 35 cm.

The system can further include the catheter having the lumen and thedistal end. The catheter can include a flexible distal luminal portionhaving a proximal end, a proximal end region, and a proximal opening.The lumen can extend between the proximal end and the distal end. Thecatheter can further include a proximal extension extending proximallyfrom a point of attachment adjacent the proximal opening. The proximalextension can be less flexible than the flexible distal luminal portionand can be configured to control movement of the catheter. The proximalextension can have an outer diameter at the point of attachment that issmaller than an outer diameter of the distal luminal portion at thepoint of attachment. A material hardness of the flexible distal luminalportion can transition proximally towards increasingly harder materialsup to the proximal extension. The flexible distal luminal portion caninclude a second plurality of material transitions. The flexibleelongate body can be coaxially positioned within the lumen of thecatheter such that the distal tip portion of the flexible elongate bodyextends distally beyond the distal end of the catheter such that thefirst plurality of material transitions of the flexible elongate bodyare staggered relative to and do not overlap with the second pluralityof material transitions of the flexible distal luminal portion.

The catheter can be packaged with the device coaxially positioned withinthe lumen of the catheter such that the proximal portion of the flexibleelongate body is locked with the proximal extension of the catheter. Atleast a portion of the proximal extension of the catheter can becolor-coded.

The single lumen of the flexible elongate body can be sized toaccommodate a guidewire. The flexible elongate body can include aproximal opening sized to accommodate the guidewire. The proximalopening can be located within the proximal end region of the flexibleelongate body. The proximal opening can be through a sidewall of theflexible elongate body and located a distance distal to the proximalportion coupled to the proximal end region. The distance can be about 10cm from the distal tip portion up to about 20 cm from the distal tipportion. The proximal portion can have an outer diameter that is smallerthan the outer diameter of the flexible elongate body. The proximalportion can be a hypotube. The device can be configured to be advancedtogether with the catheter after the distal end of the catheter isdistal to the petrous portion of the internal carotid artery.

In an interrelated aspect, disclosed is a method of performing a medicalprocedure in a cerebral vessel of a patient including inserting anassembled coaxial catheter system into a blood vessel of a patient. Theassembled coaxial catheter system includes a catheter and a catheteradvancement element. The catheter includes a flexible distal luminalportion having a proximal end, a proximal end region, a proximalopening, a distal end, and a lumen extending between the proximal endand the distal end; and a proximal extension extending proximally from apoint of attachment adjacent the proximal opening. The proximalextension is less flexible than the flexible distal luminal portion andis configured to control movement of the catheter. The proximalextension has an outer diameter at the point of attachment that issmaller than an outer diameter of the distal luminal portion at thepoint of attachment. The catheter advancement element includes aflexible elongate body having a proximal end region, an outer diameter,a tapered distal tip portion, a distal opening, and a single lumenextending longitudinally through the flexible elongate body to thedistal opening; and a proximal portion extending proximally from theproximal end region to a proximal-most end of the catheter advancementelement. When assembled, the catheter advancement element extendsthrough the catheter lumen and the tapered distal tip portion extendsdistal to the distal end of the distal luminal portion. The methodfurther includes advancing the assembled catheter system until thedistal end of the distal luminal portion reaches a target site withinthe cerebral vessel and the point of attachment between the distalluminal portion and the proximal extension is positioned proximal to thebrachiocephalic take-off in the aortic arch. The method further includesremoving the catheter advancement element from the lumen of thecatheter; and removing occlusive material while applying a negativepressure to the lumen of the catheter.

The distal end of the distal luminal portion can be positioned distal tothe carotid siphon when the point of attachment is positioned proximalto the brachiocephalic take-off within the aortic arch. The distalluminal portion can have a length between 35 cm and 60 cm. The proximalportion of the catheter advancement element can be coupled to theproximal end region of the flexible elongate body at a point ofattachment, the proximal portion extending proximally from the point ofattachment to the proximal-most end of the catheter advancement element.The proximal portion can have a single lumen extending through an entirelength of the proximal portion that communicates with the single lumenof the elongate body. The elongate body can have a length sufficient toallow the point of attachment between the elongate body and the proximalportion to remain within or proximal to the aortic arch when assembledwith the catheter. The distal end of the catheter can be positioned nearthe target site within the cerebral vessel.

The assembled catheter system can be pre-packaged with the catheteradvancement element coaxially positioned within the lumen of the distalluminal portion such that the proximal portion of the flexible elongatebody is locked with the proximal extension of the catheter. At least aportion of the proximal extension of the catheter can be color-coded.The single lumen of the flexible elongate body can be sized toaccommodate a guidewire. The flexible elongate body can include aproximal opening sized to accommodate the guidewire. The proximalopening can be located within the proximal end region of the flexibleelongate body. The proximal opening can be through a sidewall of theflexible elongate body and can be located a distance distal to theproximal portion coupled to the proximal end region. The distance can beabout 10 cm from the distal tip portion up to about 20 cm from thedistal tip portion. A hardness of the flexible elongate body cantransition proximally towards increasingly harder materials up to theproximal portion forming a first plurality of material transitions. Atleast a portion of the flexible elongate body can be formed of aplurality of layers including a reinforcement layer. The reinforcementlayer can be a braid. The braid can extend from the proximal end regionof the flexible elongate body and terminate at a point proximal to thedistal tip portion. The point can be located between 4 cm and 15 cm froma distal-most terminus of the flexible elongate body. The plurality oflayers can further include a first polymer material layer and a secondpolymer material layer. The braid can be positioned between the firstand second polymer material layers. The proximal portion can be ahypotube having a distal end coupled to the flexible elongate body. Thebraid positioned between the first and second polymer material layers ispositioned over the distal end of the hypotube.

The distal tip portion can include a material having a material hardnessthat is no more than 35 D. The proximal end region of the elongate bodycan include a material having a material hardness that is between 55 Dto 72 D. The elongate body can include a first segment including thedistal tip portion having a hardness of no more than 35 D. The elongatebody can include a second segment located proximal to the first segmenthaving a hardness of no more than 55 D. The elongate body can include athird segment located proximal to the second segment having a hardnessof no more than 72 D. The proximal portion can couple to the elongatebody within the third segment. The first segment can be unreinforced andthe third segment can be reinforced. The second segment can be at leastpartially reinforced. A reinforcement braid can extend through at leastthe third segment. The first, second, and third segments can combine toform an insert length of the elongate body. The first segment can have alength of about 4 cm to about 12.5 cm. The second segment can have alength of about 5 cm to about 8 cm. The third segment can have a lengthof about 25 cm to about 35 cm. A material hardness of the flexibledistal luminal portion can transition proximally towards increasinglyharder materials up to the proximal extension. The flexible distalluminal portion can include a second plurality of material transitions.The flexible elongate body can be coaxially positioned within the lumenof the catheter such that the distal tip portion of the flexibleelongate body extends distally beyond the distal end of the cathetersuch that the first plurality of material transitions of the flexibleelongate body are staggered relative to and do not overlap with thesecond plurality of material transitions of the flexible distal luminalportion.

In an interrelated aspect, described is a method of performing a medicalprocedure in a cerebral vessel of a patient including inserting a guidesheath into a blood vessel. The guide sheath include a lumen extendingbetween a proximal end region and a distal end region of the guidesheath, the distal end region of the guide sheath having an opening incommunication with the lumen of the guide sheath. The method includespositioning the guide sheath such that the distal end region of theguide sheath is positioned within at least to a level of the commoncarotid artery. The method includes inserting an intermediate catheterthrough the lumen of the guide sheath. The intermediate catheterincludes a lumen and a distal opening at a distal end of theintermediate catheter. The method includes advancing the intermediatecatheter such that the distal end of the intermediate catheter isadvanced through the opening of the guide sheath and beyond the distalend region of the guide sheath. The method includes inserting a distalaccess catheter through the lumen of the intermediate catheter. Thedistal access catheter includes a flexible distal luminal portion havinga proximal end, a proximal end region, a proximal opening, a distal end,and a lumen extending between the proximal end and the distal end; and aproximal extension extending proximally from a point of attachmentadjacent the proximal opening. The proximal extension is less flexiblethan the flexible distal luminal portion and is configured to controlmovement of the catheter. The proximal extension has an outer diameterat the point of attachment that is smaller than an outer diameter of theflexible distal luminal portion at the point of attachment. The methodfurther includes advancing the distal access catheter such that thedistal end of the flexible distal luminal portion is advanced throughthe distal opening of the intermediate catheter and beyond the distalend of the intermediate catheter.

The distal end region of the guide sheath can include an inflatableocclusion balloon. The method can further include inflating theocclusion balloon to occlude antegrade flow through the common carotidartery. The distal end region of the guide sheath can have an unlined,unreinforced region configured to seal onto an outer surface of theintermediate catheter. The distal access catheter can be assembled witha catheter advancement element forming an assembled coaxial cathetersystem prior to the advancing step. The catheter advancement elementincludes a flexible elongate body having a proximal end region, an outerdiameter, a tapered distal tip portion, a distal opening, and a singlelumen extending longitudinally through the flexible elongate body to thedistal opening; and a proximal portion extending proximally from theproximal end region to a proximal-most end of the catheter advancementelement.

When assembled, the catheter advancement element can extend through thelumen of the distal luminal portion and the tapered distal tip portioncan extend distal to the distal end of the distal luminal portion. Themethod can further include advancing the assembled coaxial cathetersystem until the distal end of the distal luminal portion reaches atarget site within the cerebral vessel and the point of attachmentbetween the distal luminal portion and the proximal extension ispositioned proximal to the brachiocephalic take-off in the aortic arch.The method can further include removing the catheter advancement elementfrom the lumen of the catheter; and removing occlusive material whileapplying a negative pressure to the lumen of the catheter.

The assembled catheter system can be pre-packaged with the catheteradvancement element coaxially positioned within the lumen of the distalluminal portion such that the proximal portion of the flexible elongatebody is locked with the proximal extension of the catheter. At least oneof the intermediate catheter and the distal access catheter can furtherinclude a tab to prevent over-insertion of the catheter relative to thelumen through which it extends. At least one of the intermediatecatheter and the distal access catheter can further include adistinguishable color-coded element. The single lumen of the flexibleelongate body can be sized to accommodate a guidewire. The flexibleelongate body can include a proximal opening sized to accommodate theguidewire. The proximal opening can be located within the proximal endregion of the flexible elongate body. The proximal opening can bethrough a sidewall of the flexible elongate body and can be located adistance distal to the proximal portion coupled to the proximal endregion. The distance can be about 10 cm from the distal tip portion upto about 20 cm from the distal tip portion.

The intermediate catheter can be assembled with a catheter advancementelement forming an assembled coaxial catheter system prior to theadvancing step. The catheter advancement element can include a flexibleelongate body having a proximal end region, an outer diameter, a tapereddistal tip portion, a distal opening, and a single lumen extendinglongitudinally through the flexible elongate body to the distal opening;and a proximal portion extending proximally from the proximal end regionto a proximal-most end of the catheter advancement element. Whenassembled, the catheter advancement element can extend through the lumenof the intermediate catheter and the tapered distal tip portion canextend distal to the distal end of the intermediate catheter. Theintermediate catheter can include a flexible distal luminal portion anda proximal extension extending proximally from a point of attachmentadjacent a proximal opening in the flexible distal luminal portion. Theproximal extension can be less flexible than the flexible distal luminalportion of the intermediate catheter and have an outer diameter that issmaller than an outer diameter of the proximal elongate body.

In some variations, one or more of the following can optionally beincluded in any feasible combination in the above methods, apparatus,devices, and systems. More details of the devices, systems, and methodsare set forth in the accompanying drawings and the description below.Other features and advantages will be apparent from the description anddrawings.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects will now be described in detail with referenceto the following drawings. Generally speaking the figures are not toscale in absolute terms or comparatively, but are intended to beillustrative. Also, relative placement of features and elements may bemodified for the purpose of illustrative clarity.

FIGS. 1A-1B illustrate the course of the terminal internal carotidartery through to the cerebral vasculature;

FIG. 1C illustrates the aortic arch including the take-offs of thebrachiocephalic BT, left common carotid LCC, and left subclavianarteries LSA from the aortic arch AA;

FIG. 2A is an exploded view of an implementation of an aspirationcatheter system;

FIG. 2B is an assembled view of the system of FIG. 2A;

FIG. 2C is a detail view of FIG. 2A taken at circle C-C;

FIG. 2D illustrates an implementation of an arterial access devicehaving a distal occlusion balloon;

FIG. 3 is a side view of an implementation of a catheter;

FIG. 4A is a cross-sectional view of first implementation of a proximalextension of a catheter;

FIG. 4B is a cross-sectional view of another implementation of aproximal extension of a catheter;

FIG. 4C is a cross-sectional view of the proximal extension of FIG. 4Awithin a working lumen of an access sheath;

FIG. 4D is a cross-sectional view of the proximal extension of FIG. 4Bwithin a working lumen of an access sheath having a catheter advancementelement extending therethrough;

FIG. 4E is a cross-sectional, schematic view comparing the surface areaof the proximal extension of FIG. 4A and the proximal extension of FIG.4B within the working lumen of an access sheath of FIG. 4D;

FIGS. 4F-4G are cross-sectional, schematic views comparing trapezoid-and D-shaped proximal extensions, respectively, relative to a workinglumen of an access sheath;

FIG. 5A is a side elevational view of an implementation of a catheter;

FIG. 5B is a top plan view of the catheter of FIG. 5A;

FIG. 5C is a cross-sectional view of the catheter taken along line C-Cof FIG. 5B;

FIG. 5D is a cross-sectional view of the catheter taken along line D-Dof FIG. 5B;

FIGS. 5E-5F are partial perspective views of the catheter of FIG. 5A;

FIG. 6A is a side elevational view of an implementation of a catheter;

FIG. 6B is a top plan view of the catheter of FIG. 6A;

FIG. 6C is a cross-sectional view of the catheter taken along line C-Cof FIG. 6B;

FIG. 6D is a cross-sectional view of the catheter taken along line D-Dof FIG. 6B;

FIGS. 6E-6F are partial perspective views of the catheter of FIG. 6A;

FIG. 7A is a side view of an implementation of a catheter advancementelement;

FIG. 7B is a cross-sectional view of the catheter advancement element ofFIG. 7A;

FIG. 7C is a detail view of FIG. 7B taken along circle C-C;

FIG. 7D is a side view of another implementation of a catheteradvancement element;

FIG. 7E is cross-sectional view of an implementation of a proximalportion the catheter advancement element of FIG. 7D;

FIGS. 7F-7J are various views of an implementation of a proximal hub forcoupling to the proximal portion shown in FIG. 7E;

FIG. 8A is a side view of an implementation of a catheter;

FIG. 8B is a schematic cut-away view of the distal end region of thecatheter of FIG. 8A;

FIG. 8C is a schematic cross-sectional view of the distal end region ofthe catheter of FIG. 8A;

FIG. 9A-9C are various views of a proximal extension connector;

FIG. 10A is a schematic cross-sectional view of an implementation of acatheter advancement element;

FIG. 10B is a schematic cross-sectional view of a distal end region ofthe catheter advancement element of FIG. 10A;

FIG. 10C is a schematic cross-sectional view of a middle region of thecatheter advancement element of FIG. 10A;

FIG. 11 is a schematic of an implementation of a catheter aligned withan implementation of a catheter advancement element illustratingstaggered material transitions;

FIG. 12 is a tear-away disc coupler.

It should be appreciated that the drawings are for example only and arenot meant to be to scale. It is to be understood that devices describedherein may include features not necessarily depicted in each figure.

DETAILED DESCRIPTION

Navigating the carotid anatomy in order to treat various neurovascularpathologies at the level of the cerebral arteries, such as acuteischemic stroke (AIS), requires catheter systems having superiorflexibility and deliverability. The internal carotid artery (ICA) arisesfrom the bifurcation of the common carotid artery (CCA) at the level ofthe intervertebral disc between C3 and C4 vertebrae. As shown in FIG.1A, the course of the ICA is divided into four parts—cervical Cr,petrous Pt, cavernous Cv and cerebral Cb parts. In the anteriorcirculation, the consistent tortuous terminal carotid is locked into itsposition by bony elements. The cervical carotid Cr enters the petrousbone and is locked into a set of turns as it is encased in bone. Thecavernous carotid is an artery that passes through a venous bed, thecavernous sinus, and while flexible, is locked as it exits the cavernoussinus by another bony element, which surrounds and fixes the entry intothe cranial cavity. Because of these bony points of fixation, thepetrous and cavernous carotid (Pt and Cv) and above are relativelyconsistent in their tortuosity. The carotid siphon CS is an S-shapedpart of the terminal ICA. The carotid siphon CS begins at the posteriorbend of the cavernous ICA and ends at the ICA bifurcation into theanterior cerebral artery ACA and middle cerebral artery MCA. Theophthalmic artery arises from the cerebral ICA, which represents acommon point of catheter hang-up in accessing the anterior circulation.The MCA is initially defined by a single M1 segment and then furtherbifurcates in two or three M2 segments and then further arborizes tocreate M3 segments. These points of catheter hang up can significantlyincrease the amount of time needed to restore blood perfusion to thebrain, which in the treatment of AIS is a disadvantage with severeconsequences.

With advancing age, the large vessels often enlarge and lengthen. Fixedproximally and distally, the cervical internal carotid artery oftenbecomes tortuous with age. The common carotid artery CCA is relativelyfixed in the thoracic cavity as it exits into the cervical area by theclavicle. The external and internal carotid arteries ECA, ICA are notfixed relative to the common carotid artery CCA, and thus they developtortuosity with advancing age with lengthening of the entire carotidsystem. This can cause them to elongate and develop kinks and tortuosityor, in worst case, a complete loop or so-called “cervical loop”. Ifcatheters used to cross these kinked or curved areas are too stiff orinflexible, these areas can undergo a straightening that can cause thevessel to wrap around or “barbershop pole” causing focused kinking andfolding of the vessel. These sorts of extreme tortuosity also cansignificantly increase the amount of time needed to restore bloodperfusion to the brain, particularly in the aging population. In certaincircumstances, the twisting of vessels upon themselves or if theuntwisted artery is kinked, normal antegrade flow may be reduced to astandstill creating ischemia. Managing the unkinking or unlooping thevessels such as the cervical ICA can also increase the time it takes toperform a procedure.

A major drawback of current catheter systems and methods for strokeintervention procedures is the amount of time required to restore bloodperfusion to the brain, including the time it takes to access theocclusive site or sites in the cerebral artery and the time it takes tocompletely remove the occlusion in the artery. Because it is often thecase that more than one attempt must be made to completely remove theocclusion, reducing the number of attempts as well as reducing the timerequired to exchange devices for additional attempts is an importantfactor in minimizing the overall time. Additionally, each attempt isassociated with potential procedural risk due to device advancement inthe delicate cerebral vasculature. Another limitation is the need formultiple operators to deliver and effectively manipulate long tri-axialsystems with multiple RHVs typically used with conventional guide anddistal access catheters.

Described herein are catheter systems for treating various neurovascularpathologies, such as acute ischemic stroke (AIS). The systems describedherein provide quick and simple single-operator access to distal targetanatomy, in particular tortuous anatomy of the cerebral vasculature at asingle point of manipulation. The medical methods, devices and systemsdescribed herein allow for navigating complex, tortuous anatomy toperform rapid and safe aspiration and removal of cerebral occlusions forthe treatment of acute ischemic stroke. The medical methods, devices andsystems described herein can also be used to deliver intracranialmedical devices, with or without aspiration for the removal of cerebralocclusions in the treatment of acute ischemic stroke. The systemsdescribed herein can be particularly useful for the treatment of AISwhether a user intends to perform stent retriever delivery alone,aspiration alone, or a combination of aspiration and stent retrieverdelivery as a frontline treatment for AIS. Further, the extremeflexibility and deliverability of the distal access catheter systemsdescribed herein allow the catheters to take the shape of the tortuousanatomy rather than exert straightening forces creating new anatomy. Thedistal access catheter systems described herein can pass throughtortuous loops while maintaining the natural curves of the anatomytherein decreasing the risk of vessel straightening. The distal accesscatheter systems described herein can thereby create a safe conduitthrough the neurovasculature maintaining the natural tortuosity of theanatomy for other catheters to traverse (e.g. interventional devicedelivery catheters). The catheters traversing the conduit need not havethe same degree of flexibility and deliverability such that if they weredelivered directly to the same anatomy rather than through the conduit,would lead to straightening, kinking, or folding of the anteriorcirculation.

While some implementations are described herein with specific regard toaccessing a neurovascular anatomy or delivery of treatment devices, thesystems and methods described herein should not be limited to this andmay also be applicable to other uses. For example, the catheter systemsdescribed herein may be used to deliver working devices to a targetvessel of a coronary anatomy, peripheral anatomy, or other vasculatureanatomy. Coronary vessels are considered herein including left and rightcoronary arteries, posterior descending artery, right marginal artery,left anterior descending artery, left circumflex artery, M1 and M2 leftmarginal arteries, and D1 and D2 diagonal branches. Any of a variety ofperipheral vessels are considered herein including the poplitealarteries, anterior tibial arteries, dorsalis pedis artery, posteriortibial arteries, and fibular artery. It should also be appreciated thatwhere the phrase “aspiration catheter” is used herein that such acatheter may be used for other purposes besides or in addition toaspiration, such as the delivery of fluids to a treatment site or as asupport catheter or distal access catheter providing a conduit thatfacilitates and guides the delivery or exchange of other devices such asa guidewire or interventional devices, such as stent retrievers.Alternatively, the access systems described herein may also be usefulfor access to other parts of the body outside the vasculature.Similarly, where the working device is described as being an expandablecerebral treatment device, stent retriever or self-expanding stent otherinterventional devices can be delivered using the delivery systemsdescribed herein.

Referring now to the drawings, FIGS. 2A-2B illustrate a system 100including devices for accessing and removing a cerebral occlusion totreat acute ischemic stroke from an access site. The system 100 can be asingle operator system such that each of the components and systems canbe delivered and used together by one operator through a single point ofmanipulation requiring minimal hand movements. As will be described inmore detail below, all wire and catheter manipulations can occur at orin close proximity to a single rotating hemostatic valve (RHV) 434 ormore than a single RHV co-located in the same device. The system 100 caninclude one or more of a catheter 200, a catheter advancement element300, and an access guide sheath 400, each of which will be described inmore detail below. The catheter 200 is configured to be received throughthe guide sheath 400 and is designed to have exceptional deliverability.The catheter 200 can be a spined, distal access catheter co-axial with alumen of the guide sheath 400 thereby providing a step-up in innerdiameter within the conduit. The catheter 200 can be delivered using acatheter advancement element 300 inserted through a lumen 223 of thecatheter 200 forming a catheter delivery system 150. The system 100 canbe a distal access system that can create a variable length from pointof entry at the percutaneous arteriotomy (e.g. the femoral artery orother point of entry) to the target control point of the distalcatheter. Conventional distal access systems for stroke interventiontypically include a long guide sheath or guide catheter placed through ashorter “introducer” sheath (e.g. 11-30 cm in length) at the groin. Thelong guide sheath is typically positioned in the ICA to supportneurovascular interventions including stroke embolectomy (sometimesreferred to as “thrombectomy”). For added support, these can be advancedup to the bony terminal petrous and rarely into the cavernous or clinoidor supraclinoid terminal ICA when possible. To reach targets in the M1or M2 distribution for ADAPT/MAT or Solumbra/SMAT approaches, anadditional catheter may be inserted through the long guide catheter.These catheters are typically large-bore aspiration catheters that canbe, for example 130 cm in length or longer. As will be described in moredetail below, the distal access systems 100 described herein can beshorter, for example, only 115 cm in length when taken as a system asmeasured from the access point, typically the common femoral artery.Additionally, the single operator can use the systems described hereinby inserting them through a single rotating hemostatic valve (RHV) 434on the guide sheath 400 or more than one RHV co-located in the samedevice such as a dual-headed RHV. Thus, what was once a two-personprocedure can be a one-person procedure.

Each of the various components of the various systems will now bedescribed in more detail.

Access Guide Sheath

Now with respect to FIGS. 2A-2D, the distal access system 100 caninclude an access guide sheath 400 having a body 402 through which aworking lumen extends from a proximal hemostasis valve 434 coupled to aproximal end region 403 of the body 402 to a distal opening 408 of adistal end region. The working lumen is configured to receive thecatheter 200 therethrough such that a distal end of the catheter 200 canextend beyond a distal end of the sheath 400 through the distal opening408. The guide sheath 400 can be used to deliver the catheters describedherein as well as any of a variety of working devices known in the art.For example, the working devices can be configured to provide thrombotictreatments and can include large-bore catheters, aspiration embolectomy(or thrombectomy), advanced catheters, wires, balloons, retrievablestructures such as coil-tipped retrievable stents “Stentriever” as wellas permanent structures including flow diverters, and vessel supportimplants including balloon expandable stents, self-expanding stents, andmesh sleeves. The guide sheath 400 in combination with the catheter 200can be used to apply distal aspiration as will be described in moredetail below.

The guide sheath 400 can be any of a variety of commercially availableguide sheaths. For example, the guide sheath 400 can have an ID between0.087″-0.089″ such as the Cook SHUTTLE 6 F (Cook Medical, Inc.,Bloomington, Ind.), Terumo DESTINATION 6 F (Terumo Europe NV), CordisVISTA BRITE TIP (Cordis Corp., Hialeah, Fla.), and Penumbra NEURON MAX088 (Penumbra, Inc., Alameda, Calif.), or comparable commerciallyavailable guiding sheath. Generally, sheath sizes are described hereinusing the French (F) scale. For example, where a sheath is described asbeing 6 French, the inner diameter of that sheath is able to receive acatheter having a 6 F outer diameter, which is about 1.98 mm or 0.078″.A catheter may be described herein as having a particular size in Frenchto refer to the compatibility of its inner diameter to receive an outerdiameter of another catheter. A catheter may also be described herein ashaving a particular size in French to refer to its outer diameter beingcompatible with another catheter having a particular inner diameter.

Again with respect to FIGS. 2A-2D, the catheter body 402 can extend froma proximal furcation or rotating hemostatic valve (RHV) 434 at aproximal end region 403 to a tip 406 at a distal end of the body 402.The proximal RHV 434 may include one or more lumens molded into aconnector body to connect to the working lumen of the body 402 of theguide sheath 400. As described above, the working lumen can receive thecatheter 200 and/or any of a variety of working devices for delivery toa target anatomy. The RHV 434 can be constructed of thick-walled polymertubing or reinforced polymer tubing. The RHV 434 allows for theintroduction of devices through the guide sheath 400 into thevasculature, while preventing or minimizing blood loss and preventingair introduction into the guide sheath 400. The RHV 434 can be integralto the guide sheath 400 or the guide sheath 400 can terminate on aproximal end in a female Luer adaptor to which a separate hemostasisvalve component, such as a passive seal valve, a Tuohy-Borst valve orrotating hemostasis valve may be attached. The RHV 434 can have anadjustable opening that is open large enough to allow removal of devicesthat have adherent clot on the tip without causing the clot to dislodgeat the RHV 434 during removal. Alternately, the RHV 434 can be removablesuch as when a device is being removed from the sheath 400 to preventclot dislodgement at the RHV 434. The RHV 434 can be a dual RHV.

The RHV 434 can form a Y-connector on the proximal end 403 of the sheath400 such that the first port of the RHV 434 can be used for insertion ofa working catheter into the working lumen of the sheath 400 and a secondport into arm 412 can be used for another purpose. For example, asyringe or other device can be connected at arm 412 via a connector 432to deliver a forward drip, a flush line for contrast or salineinjections through the body 402 toward the tip 406 and into the targetanatomy. Arm 412 can also connect to a large-bore aspiration line and anaspiration source (not shown) such as a syringe or pump to draw suctionthrough the working lumen. The aspiration source can be an active sourceof aspiration such as an aspiration pump, a regular or locking syringe,a hand-held aspirator, hospital suction, or the like, configured to drawsuction through the working lumen. The aspiration source can be alocking syringe (for example a VacLok syringe) attached to a flowcontroller. The arm 412 can also allow the guide sheath 400 to beflushed with saline or radiopaque contrast during a procedure. Theworking lumen can extend from a distal end to a working proximal port ofthe proximal end region 403 of the catheter body 402.

The length of the catheter body 402 is configured to allow the distaltip 406 of the body 402 to be positioned as far distal in the internalcarotid artery (ICA), for example, from a transfemoral approach withadditional length providing for adjustments if needed. In someimplementations (e.g. femoral or radial percutaneous access), the lengthof the body 402 can be in the range of 80 to 90 cm although the of thebody 402 can be longer, for example, up to about 100 cm or up to about105 cm or up to about 117 cm total. In implementations, the body 402length is suitable for a transcarotid approach to the bifurcation of thecarotid artery, in the range of 20-25 cm. In further implementations,the body 402 length is suitable for a percutaneous transcarotid approachto the CCA or proximal ICA, and is in the range of 10-15 cm. The body402 is configured to assume and navigate the bends of the vasculaturewithout kinking, collapsing, or causing vascular trauma, even, forexample, when subjected to high aspiration forces. The point ofinsertion for the guide sheath 400 can vary including femoral, carotid,radial, brachial, ulnar, or subclavian arteries. The lengths of the body402 described herein can be modified to accommodate different accesspoints for the guide sheath 400. For example a body 402 of a guidesheath 400 for entry through the femoral artery near the groin may belonger than a body 402 of a guide sheath 400 for entry through thesubclavian artery.

The tip 406 of the guide sheath 400 can have a same or similar outerdiameter as a section of the body 402 leading up to the distal end.Accordingly, the tip 406 may have a distal face orthogonal to alongitudinal axis passing through the body 402 and the distal face mayhave an outer diameter substantially equal to a cross-sectional outerdimension of the body 402. In an implementation, the tip 406 includes achamfer, fillet, or taper, making the distal face diameter slightly lessthan the cross-sectional dimension of the body 402. In a furtherimplementation, the tip 406 may be an elongated tubular portionextending distal to a region of the body 402 having a uniform outerdiameter such that the elongated tubular portion has a reduced diametercompared to the uniform outer diameter of the body 402. Thus, the tip406 can be elongated or can be more bluntly shaped. Accordingly, the tip406 may be configured to smoothly track through a vasculature and/or todilate vascular restrictions as it tracks through the vasculature. Theworking lumen may have a distal end forming a distal opening 408.

The guide sheath 400 may include a tip 406 that tapers from a section ofthe body 402 leading up to the distal end. That is, an outer surface ofthe body 402 may have a diameter that reduces from a larger dimension toa smaller dimension at a distal end. For example, the tip 406 can taperfrom an outer diameter of approximately 0.114″ to about 0.035″ or fromabout 0.110″ to about 0.035″ or from about 0.106″ to about 0.035″. Theangle of the taper of the tip 406 can vary depending on the length ofthe tapered tip 406. For example, in some implementations, the tip 406tapers from 0.110″ to 0.035″ over a length of approximately 50 mm.

In an implementation, the guide sheath 400 includes one or moreradiopaque markers 411. The radiopaque markers 411 can be disposed nearthe distal tip 406. For example, a pair of radiopaque bands may beswaged, painted, embedded, or otherwise disposed in or on the body 402.In some implementations, the radiopaque markers 411 include a bariumpolymer, tungsten polymer blend, tungsten-filled or platinum-filledmarker that maintains flexibility of the distal end of the device andimproves transition along the length of the guide sheath 400 and itsresistance to kinking. In some implementations, the radiopaque marker411 is a tungsten-loaded PEBAX or polyurethane that is heat welded tothe body 402. The markers 411 are shown in the figures as rings around acircumference of one or more regions of the body 402. However, themarkers 411 need not be rings and can have other shapes or create avariety of patterns that provide orientation to an operator regardingthe position of the distal opening 408 within the vessel. Accordingly,an operator may visualize a location of the distal opening 408 underfluoroscopy to confirm that the distal opening 408 is directed toward atarget anatomy where a catheter 200 is to be delivered. For example,radiopaque marker(s) 411 allow an operator to rotate the body 402 of theguide sheath 400 at an anatomical access point, e.g., a groin of apatient, such that the distal opening provides access to an ICA bysubsequent working device(s), e.g., catheters and wires advanced to theICA. In some implementations, the radiopaque marker(s) 411 includeplatinum, gold, tantalum, tungsten or any other substance visible underan x-ray fluoroscope. Any of the components of the systems describedherein can incorporate radiopaque markers as described above.

In some implementations, the guide sheath 400 can have performancecharacteristics similar to other sheaths used in carotid access and AISprocedures in terms of kinkability, radiopacity, column strength, andflexibility. The inner liners can be constructed from a low frictionpolymer such as PTFE (polytetrafluoroethylene) or FEP (fluorinatedethylene propylene) to provide a smooth surface for the advancement ofdevices through the inner lumen. An outer jacket material can providemechanical integrity to the inner liners and can be constructed frommaterials such as PEBAX, thermoplastic polyurethane, polyethylene,nylon, or the like. A third layer can be incorporated that can providereinforcement between the inner liner and the outer jacket. Thereinforcement layer can prevent flattening or kinking of the inner lumenof the body 402 to allow unimpeded device navigation through bends inthe vasculature as well as aspiration or reverse flow. The body 402 canbe circumferentially reinforced. The reinforcement layer can be madefrom metal such as stainless steel, Nitinol, Nitinol braid, helicalribbon, helical wire, cut stainless steel, or the like, or stiff polymersuch as PEEK. The reinforcement layer can be a structure such as a coilor braid, or tubing that has been laser-cut or machine-cut so as to beflexible. In another implementation, the reinforcement layer can be acut hypotube such as a Nitinol hypotube or cut rigid polymer, or thelike. The outer jacket of the body 402 can be formed of increasinglysofter materials towards the distal end. For example, proximal region ofthe body 402 can be formed of a material such as Nylon, a region of thebody 402 distal to the proximal region of the body 402 can have ahardness of 72 D whereas areas more distal can be increasingly moreflexible and formed of materials having a hardness of 55 D, 45 D, 35 Dextending towards the distal tip 406, which can be formed of a materialhaving a hardness of no more than 35 D and in some implementationssofter than 35 D. The body 402 can include a hydrophilic coating.

The flexibility of the body 402 can vary over its length, withincreasing flexibility towards the distal portion of the body 402. Thevariability in flexibility may be achieved in various ways. For example,the outer jacket may change in durometer and/or material at varioussections. A lower durometer outer jacket material can be used in adistal section of the guide sheath compared to other sections of theguide sheath. Alternately, the wall thickness of the jacket material maybe reduced, and/or the density of the reinforcement layer may be variedto increase the flexibility. For example, the pitch of the coil or braidmay be stretched out, or the cut pattern in the tubing may be varied tobe more flexible. Alternately, the reinforcement structure or thematerials may change over the length of the elongate body 402. Inanother implementation, there is a transition section between thedistal-most flexible section and the proximal section, with one or moresections of varying flexibilities between the distal-most section andthe remainder of the elongate body 402. In this implementation, thedistal-most section is about 2 cm to about 5 cm, the transition sectionis about 2 cm to about 10 cm and the proximal section takes up theremainder of the sheath length.

The different inner diameters of the guide sheaths 400 can be used toreceive different outer diameter catheters 200. In some implementations,the working lumen of a first guide sheath 400 can have an inner diametersized to receive a 6 F catheter and the working lumen of a second guidesheath 400 can have an inner diameter sized to receive an 8 F catheter.In some implementations, the distal region of the guide sheath 400 canhave an inner diameter of about 0.087″ to 0.088″. The guide sheaths 400can receive catheters having an outer diameter that is snug to theseinner diameter dimensions. The guide sheath 400 (as well as any of thevariety of components used in combination with the sheath 400) can be anover-the-wire (OTW) or rapid exchange type device, which will bedescribed in more detail below.

As described above, the sheath 400 can include a body 402 formed ofgenerally three layers, including a lubricious inner liner, areinforcement layer, and an outer jacket layer. The reinforcement layercan include a braid to provide good torqueability optionally overlaid bya coil to provide good kink resistance. In sheaths where thereinforcement layer is a braid alone, the polymers of the outer jacketlayer can be generally higher durometer and thicker to avoid issues withkinking. The wall thickness of such sheaths that are braid alone withthicker polymer can be about 0.011″. The wall thickness of the sheaths400 described herein having a braid with a coil overlay provide bothtorqueability and kink resistance and can have a generally thinner wall,for example, a wall thickness of about 0.0085″. The proximal end outerdiameter can thereby be reduced to about 0.107″ outer diameter. Thus,the sheath 400 is a high performance sheath 400 that has good torque andkink resistance with a thinner wall providing an overall lower profileto the system. The thinner wall and lower profile allows for a smallerinsertion hole through the vessel without impacting overall lumen size.In some implementations, the wall thickness of the guide sheath 400 canslowly step down to be thinner towards a distal end of the sheathcompared to a proximal end.

The guide sheath 400 may include a distal tip 406 that is designed toseal well with an outer diameter of a catheter extending through itsworking lumen. The distal tip 406 can be formed of soft material that isdevoid of both liner and reinforcement layers. The lubricious linerlayer and also the reinforcement layer can extend through a majority ofthe body 402 except for a length of the distal tip 406 (see FIG. 2C).The length of this unlined, unreinforced portion of the distal tip 406of the sheath 400 can vary. In some implementations, the length isbetween about 3 mm to about 6 mm of the distal end region of the sheath400. Thus, the liner 409 of the sheath 400 can terminate at least about3 mm away from the distal-most terminus of the sheath 400 leaving thelast 3 mm unlined soft material forming the distal tip 406. In someimplementations, the coil and braid of the reinforcement layer can havetheir ends held in place by a radiopaque markers 411, such as a markerband positioned near a distal-most terminus of the sheath 400. The linerlayer 409 can extend at least a length distal to the marker band 411before terminating, for example, a length of about 1 mm. The staggeredtermination of the wall layers can aid in the transition from the markerband 411 to the soft polymer material 407 of the distal tip 406. Thesoft polymer material 407 can extend a length beyond the liner layer409. The unlined, soft material 407 forming the distal tip 406 can be aPEBAX material having a durometer of no more than about 40 D, no morethan about 35 D, no more than about 62 A, or no more than about 25 D.The softness of the material and the length of this unlined distal tip406 of the sheath 400 can vary. Generally, the material is soft enoughto be compressed down onto the outer diameter of the catheter 200extending through the lumen of the sheath 400, such as upon applicationof a negative pressure through the lumen. The length of this unlined,unreinforced region 407 of the distal tip 406 is long enough to providea good seal, but not so long as to cause problems with according orfolding over during relative sliding between the sheath 400 and thecatheter 200 that might blocking the sheath lumen or negativelyimpacting slidability of the catheter 200 within the sheath lumen.

The distal tip 406 can have an inner diameter that approaches the outerdiameter of the catheter 200 that extends through the sheath 400. Insome implementations, the inner diameter of the distal tip 406 can varydepending on what size catheter is to be used. For example, the innerdiameter of the sheath at the distal tip 406 can be about 0.106″ whenthe outer diameter of the catheter near the proximal end is about 0.101″such that the difference in diameters is about 0.005″. Upon applicationof a vacuum, the soft unlined and unreinforced distal tip 406 can moveto eliminate this 0.005″ gap and compress down onto the outer diameterof the catheter 200 near its proximal end region upon extension of thecatheter 200 out its distal opening 408. The difference between theinner diameter of the distal tip 406 and the outer diameter of thecatheter can be between about 0.002″-0.006″. The inner diameter of thedistal tip 406 can also be tapered such the inner diameter at thedistal-most terminus of the opening 408 is only 0.001″ to 0.002″ largerthan the outer diameter of the proximal end of the catheter 200extending through the working lumen. In some implementations, the distaltip 406 is shaped such that the walls are beveled at an angle relativeto a central axis of the sheath 400, such as about 60 degrees.

In some instances it is desirable for the sheath body 402 to also beable to occlude the artery in which it is positioned, for example,during procedures that may create distal emboli. Occluding the arterystops antegrade blood flow and thereby reduces the risk of distal embolithat may lead to neurologic symptoms such as TIA or stroke. FIG. 2Dshows an arterial access device or sheath 400 that has a distalocclusion balloon 440 that upon inflation occludes the artery at theposition of the sheath distal tip 406. At any point in a procedure, forexample, during removal of an occlusion by aspiration and/or delivery ofa stentriever or other interventional device, the occlusion balloon 440can be inflated to occlude the vessel to reduce the risk of distalemboli to cerebral vessels. The sheath 400 can include an inflationlumen configured to deliver a fluid for inflation of the occlusionballoon 440 in addition to the working lumen of the sheath 400. Theinflation lumen can fluidly connect the balloon 440, for example, to arm412 on the proximal adaptor. This arm 412 can be attached to aninflation device such as a syringe to inflate the balloon 440 with afluid when vascular occlusion is desired. The arm 412 may be connectedto a passive or active aspiration source to further reduce the risk ofdistal emboli.

According to some implementations, the length of the guide sheath 400 islong enough to access the target anatomy and exit the arterial accesssite with extra length outside of a patient's body for adjustments. Forexample, the guide sheath 400 (whether having a distal occlusion balloon440 or not) can be long enough to access the petrous ICA from thefemoral artery such that an extra length is still available foradjustment. The guide sheath 400 can be a variety of sizes to acceptvarious working devices and can be accommodated to the operator'spreference. For example, current MAT and SMAT techniques describedelivering aspiration catheters having inside diameters of 0.054″-0.072″to an embolus during AIS. Accordingly, the working lumen of the guidesheath 400 can be configured to receive the catheter 200 as well asother catheters or working devices known in the art. For example, theworking lumen can have an inner diameter sized to accommodate at least 6French catheters (1.98 mm or 0.078″ OD), or preferably at least 6.3French catheters (2.079 mm or 0.082″ OD). The inner diameter of theguide sheath 400, however, may be smaller or larger to be compatiblewith other catheter sizes. In some implementations, the working lumencan have an inner diameter sized to accommodate 7 French (2.31 mm or0.091″ OD) catheters or 8 French (2.64 mm or 0.104″ OD) or largercatheters. In some implementations, the working lumen can have an innerdiameter that is at least about 0.054″ up to about 0.070″, 0.071″,0.074″, 0.087″, 0.088″, or 0.100″ and thus, is configured to receive acatheter 200 having an outer diameter that fits snug with thesedimensions. Regardless of the length and inner diameter, the guidesheath 400 is resistant to kinking during distal advancement through thevasculature.

The working lumen included in the sheath 400 can be sized to receive itsrespective working devices in a sliding fit. The working lumen may havean inner diameter that is at least 0.001 inch larger than an outerdiameter of any catheter 200 it is intended to receive, particularly ifthe catheter 200 is to be used for aspiration as will be described inmore detail below. As described in more detail below, the catheter 200can include a slit 236 in the luminal portion 222 configured to widenslightly upon application of suction from an aspiration source andimprove sealing between the catheter 200 and the guide sheath 400.Additionally or alternatively, the distal tip 406 of the sheath 400 canbe designed to move downward onto the outer diameter of the catheter 200to improve sealing, as described above. The strength of the sealachieved allows for a continuous aspiration lumen from the distal tip ofthe catheter 200 to a proximal end 403 of the guide sheath 400 where itis connected to an aspiration source, even in the presence of lowersuction forces with minimal to no leakage. Generally, when there isenough overlap between the catheter 200 and the guide sheath 400 thereis no substantial leakage. However, when trying to reach distal anatomy,the catheter 200 may be advanced to its limit and the overlap betweenthe catheter 200 and the guide sheath 400 is minimal. Thus, additionalsealing can be desirable to prevent leakage around the catheter 200 intothe sheath 400. The sealing between the catheter 200 and the guidesheath 400 can prevent this leakage upon maximal extension of catheter200 relative to sheath 400.

Distal Access Catheter

Again with respect to FIGS. 2A-2B and also FIGS. 3, and 8A-8C, thedistal access system 100 can include a distal access or support catheter200 configured to extend through and out the distal end of the guidesheath 400. FIG. 3 illustrates a side elevational view of animplementation of the catheter 200. The catheter 200 can include arelatively flexible, distal luminal portion 222 coupled to a more rigid,kink-resistant proximal extension 230. The term “control element” asused herein can refer to a proximal region configured for a user tocause pushing movement in a distal direction as well as pulling movementin a proximal direction. The control elements described herein may alsobe referred to as spines, tethers, push wires, push tubes, or proximalextensions having any of a variety of configurations. The proximalextension can be hollow or tubular element. The proximal extension canalso be solid and have no inner lumen, such as a solid rod, ribbon, orother solid wire type element. Generally, the proximal extensionsdescribes herein are configured to move its respective component (towhich it may be attached or integral) in a bidirectional manner througha lumen.

The catheter 200 provides a quick way to access stroke locations withsimplicity even through the extreme tortuosity of the cerebralvasculature. The catheters described herein have a degree of flexibilityand deliverability that makes them optimally suitable to be advancedthrough the cerebral vascular anatomy without kinking or ovalizing evenwhen navigating hairpin turns. For example, the distal luminal portion222 can perform a 180 degree turn (see turn T shown in FIG. 1B near thecarotid siphon) and maintain a folded width across of 4.0 mm withoutkinking or ovalizing. Further, the distal luminal portion 222 has adegree of flexibility that maintains the natural tortuosity of thevessels through which it is advanced without applying straighteningforces such that the natural shape and curvature of the anatomy ismaintained during use. The catheter 200, particularly in combinationwith a catheter advancement element 300, which will be described in moredetail below, provides an extended conduit beyond the guide sheath 400having exceptional deliverability through convoluted anatomy that allowsfor delivering aspirational forces to a target stroke site as well asfor the delivery of stroke interventional devices such as anothercatheter, or a device such as a stent retriever, stent, flow diverter orother working devices.

An inner lumen 223 extends through the luminal portion 222 between aproximal end and a distal end of the luminal portion 222. The innerlumen 223 of the catheter 200 can have a first inner diameter and theworking lumen of the guide sheath 400 can have a second, larger innerdiameter. Upon insertion of the catheter 200 through the working lumenof the sheath 400, the lumen 223 of the catheter 200 can be configuredto be fluidly connected and contiguous with the working lumen of thesheath 400 such that fluid flow into and/or out of the system 100 ispossible, such as by applying suction from an aspiration source coupledto the system 100 at a proximal end. The combination of sheath 400 andcatheter 200 can be continuously in communication with the bloodstreamduring aspiration at the proximal end with advancement and withdrawal ofcatheter 200.

The spined catheter system can create advantages for distal access overconventional catheters particularly in terms of aspiration. The stepchange in the internal diameter of the catheter column creates a greatadvantage in aspiration flow and force that can be generated by thespined catheter 200 in combination with the conventional guide catheter.For example, where a spined catheter 200 with a 0.070″ internal diameteris paired with a standard 6 F outer diameter/0.088″ internal diameterguide catheter (e.g. Penumbra Neuron MAX 088) can create aspirationphysics where the 0.088″ catheter diameter will predominate and create a0.080 equivalent flow in the entire system.

In addition to aspiration procedures, the catheter 200 and distal accesssystem 100 can be used for delivery of tools and interventional workingdevices. As will be described in more detail below, a typical stentretriever to be delivered through the catheter 200 can have a push wirecontrol element of 180 cm. The distal access system 100 having a spinedsupport catheter 200 allows for reaching distal stroke sites using muchshorter lengths (e.g. 120 cm-150 cm). The overall length can be asimportant as diameter and radius on aspiration through the catheter. Theshorter lengths in combination with the elimination of the multiple RHVstypical in tri-axial systems allows for a single-operator use.

Where the catheter is described herein as an aspiration catheter itshould not be limited to only aspiration. Similarly, where the catheteris described herein as a way to deliver a stent retriever or otherworking device it should not be limited as such. It should also beappreciated that the systems described herein can be used to performprocedures that incorporate a combination of treatments. For example,the catheter 200 can be used for the delivery of a stent retrieverdelivery system, optionally in the presence of aspiration through thecatheter 200. As another example, a user may start out performing afirst interventional procedure using the systems described herein, suchas aspiration thrombectomy, and switch to another interventionalprocedure, such as delivery of a stent retriever or implant.

It should also be appreciated that the catheter 200 need not be spinedor include the proximal extension 230 and instead can be a non-spined,conventional catheter having a uniform diameter. The terms “supportcatheter”, “spined catheter”, “distal access catheter”, “aspirationcatheter,” and “intermediate catheter” may be used interchangeablyherein.

It is desirable to have a catheter 200 having an inner diameter that isas large as possible that can be navigated safely to the site of theocclusion, in order to optimize the aspiration force in the case ofaspiration and/or provide ample clearance for delivery of a workingdevice. A suitable size for the inner diameter of the distal luminalportion 222 may range between 0.040″ and 0.100″, or more preferablybetween 0.054″ and 0.088″, depending on the patient anatomy and the clotsize and composition. The outer diameter of the distal luminal portion222 can be sized for navigation into cerebral arteries, for example, atthe level of the M1 segment or M2 segment of the cerebral vessels. Theouter diameter (OD) should be as small as possible while stillmaintaining the mechanical integrity of the catheter 200. In animplementation, the difference between the OD of distal luminal portion222 of the catheter 200 and the inner diameter of the working lumen ofthe guide sheath 400 is between 0.001″ and 0.002″. In anotherimplementation, the difference is between 0.001″ and 0.004″. Theclearance between inner diameter of the guide sheath 400 and the outerdiameter of the catheter 200 can vary throughout the length of thecatheter 200. For example, the distal luminal portion 222 of thecatheter 200 can have localized regions of enlarged outer diametercreating localized low clearance regions (e.g., about 0.001″ difference)configured for localized sealing upon application of aspiration pressurethrough the system.

In some implementations, the distal luminal portion 222 of the catheter200 has an outer diameter (OD) configured to fit through a 6 Fintroducer sheath (0.070″-0.071″) and the lumen 223 has an innerdiameter (ID) that is sized to receive a 0.054″ catheter. In someimplementations, the distal luminal portion 222 of the catheter 200 hasan OD configured to fit through an 8 F introducer sheath (0.088″) andthe lumen 223 has an ID that is sized to receive a 0.070″ or 0.071″catheter. In some implementations, the OD of the distal luminal portion222 is 2.1 mm and the lumen 223 has an ID that is 0.071″. In someimplementations, the lumen 223 has an ID that is 0.070″ to 0.073″. Theouter diameter of the guide sheath 400 can be suitable for insertioninto at least the carotid artery, with a working lumen suitably sizedfor providing a passageway for the catheter 200 to treat an occlusiondistal to the carotid artery towards the brain. In some implementations,the ID of the working lumen can be about 0.074″ and the OD of the bodyof the guide sheath 400 can be about 0.090″, corresponding to a 5 Frenchsheath size. In some implementations, the ID of the working lumen can beabout 0.087″ and the OD of the body of the guide sheath 400 can be about0.104″, corresponding to a 6 French sheath size. In someimplementations, the ID of the working lumen can be about 0.100″ and theOD of the body of the guide sheath 400 can be about 0.117″,corresponding to a 7 French sheath size. In some implementations, theguide sheath 400 ID is between 0.087″ and 0.088″ and the OD of thedistal luminal portion 222 of the catheter 200 is approximately 0.082″and 0.086″ such that the difference in diameters is between 0.001″ and0.005″.

Smaller or larger sheath sizes are considered. For example, in someimplementations the ID of the lumen 223 is about 0.088″ and the OD ofthe distal luminal portion is between 0.101″-0.102″. However, aconventional 7 French sheath has an ID that is only about 0.100″ and aconventional 8 French sheath has an ID that is about 0.113″ such that itwould not provide a suitable sealing fit with the OD of the distalluminal portion of the catheter for aspiration embolectomy (i.e. 0.011″clearance). Thus, the guide sheath 400 can be designed to have an innerdiameter that is better suited for the 0.088″ catheter, namely between0.106″-0.107″. Additionally, the 0.088″ catheter can have a step-up inOD from 0.101″-0.102″ to about 0.105″-0.107″ OD near a proximal endregion to provide a localized area optimized for sealing with the guidesheath during application of high pressure.

In an implementation, the luminal portion 222 of the catheter 200 has auniform diameter from a proximal end to a distal end. In otherimplementations, the luminal portion 222 of the catheter 200 is taperedand/or has a step-down towards the distal end of the distal luminalportion 222 such that the distal-most end of the catheter 200 has asmaller outer diameter compared to a more proximal region of thecatheter 200, for example, near where the distal luminal portion 222seals with the guide sheath 400. In another implementation, the luminalportion 222 of the catheter OD steps up at or near an overlap portion tomore closely match the sheath inner diameter as will be described inmore detail below. This step-up in outer diameter can be due to varyingthe wall thickness of the catheter 200. For example, the catheter 200can have a wall thickness that is slightly thicker near the proximal endto provide better sealing with the sheath compared to a wall thicknessof the catheter 200 near the distal end. The catheter 200 can have athicker wall at this location while maintaining a uniform innerdiameter. This implementation is especially useful in a system with morethan one catheter suitable for use with a single access sheath size.Smaller or larger sheath sizes are considered herein. In someimplementations, a thicker wall can be created by embedding a radiopaquematerial (e.g. tungsten) such that the localized step-up in OD can bevisualized during a procedure. The catheter 200 may have a step-up inouter diameter near the proximal end region that does not result from athicker wall. For example, the inner diameter of the lumen may alsostep-up such that the wall thickness remains uniform, but the lumen sizeincreases thereby increasing the overall OD at this location.

The length of the luminal portion 222 can be shorter than a length ofthe working lumen of the guide sheath 400 such that upon advancement ofthe luminal portion 222 towards the target location results in anoverlap region 348 between the luminal portion 222 and the working lumen(see FIG. 2B). The length of the overlap region 348 can vary dependingon the length of the distal luminal portion 222 and the distance to thetarget location relative to the distal end of the guide sheath 400.Taking into account the variation in occlusion sites and sites where theguide sheath 400 distal tip 406 may be positioned, the length of theluminal portion 222 may range from about 10 cm to about 80 cm, orbetween 35 cm to about 74 cm, or between about 45 cm to about 60 cm. Insome implementations, the distal luminal portion 222 of the catheter 200can be between 20-45 cm and the proximal extension 230 of the catheter200 can be between about 90 cm to about 100 cm such that the catheter200 can have a total working length that is approximately 115 cm. Thebody 402 of the guide sheath 400 can be between 80 cm to about 90 cm. Inother implementations, the working length of the catheter 200 between aproximal end of the catheter to a distal end of the catheter can begreater than 115 cm up to about 130 cm. In some implementations, thecatheter 200 can have a working length greater than 130 cm between aproximal tab 234 (or proximal hub) and the distal tip, the distalluminal portion 222 can have a shaft length of about 40 cm±3 cm. Thedistal luminal portion 222 can have a shaft length that is at leastabout 45 cm up to a length that is shorter than the working length ofthe sheath 400. The body 402 of the guide sheath 400 can be betweenabout 80 cm to about 90 cm.

The length of the luminal portion 222 can be less than the length of thebody 402 of the guide sheath 400 such that as the catheter 200 isextended from the working lumen there remains an overlap region 348 ofthe catheter 200 and the inner diameter of the working lumen. A seal canbe formed within a region of the overlap region 348. In someimplementations, the length of the luminal portion 222 is sufficient toreach a region of the M1 segment of the middle cerebral artery (MCA) andother major vessels from a region of the internal carotid artery suchthat the proximal end region of the luminal portion 222 of the catheter200 is still maintained proximal to certain tortuous anatomies (e.g.,brachiocephalic take-off BT, the aortic arch AA, or within thedescending aorta DA). In an implementation, the luminal portion 222 ofthe catheter has a length sufficient to position its distal end withinthe M1 segment of the MCA and a proximal end within the aortic archproximal to take-offs from the arch. In an implementation, the luminalportion 222 of the catheter has a length sufficient to position itsdistal end within the M1 segment of the MCA and a proximal end withinthe descending aorta DA proximal to the aortic arch AA. Used inconjunction with a guide sheath 400 having a sheath body 402 and aworking lumen, in an implementation where the catheter 200 reaches theICA and the distance to embolus can be less than 20 cm.

The distal luminal portion 222 having a length that is less than 80 cm,for example approximately 45 cm up to about 70 cm, The distal luminalportion 222, can allow for an overlap region 348 with the body 402within which a seal forms with the sheath while still providingsufficient reach to intracranial vessels. The carotid siphon CS is anS-shaped part of the terminal ICA beginning at the posterior bend of thecavernous ICA and ending at the ICA bifurcation into the anteriorcerebral artery ACA and middle cerebral artery MCA. In someimplementations, the distal luminal portion 222 can be between about 35cm-80 cm, or between 40 cm-75 cm, or between 45 cm-60 cm long to allowfor the distal end of the catheter 200 to extend into at least themiddle cerebral arteries while the proximal control element 230 and/orthe sealing element on the proximal end region of the distal luminalportion 222 remains proximal to the carotid siphon, and preferablywithin the aorta as will be described in more detail below.

The distal luminal portion 222 can have a length measured from its pointof attachment to the proximal control element 230 to its distal end thatis long enough to extend from a region of the internal carotid artery(ICA) that is proximal to the carotid siphon to a region of the ICA thatis distal to the carotid siphon, including at least the M1 region of thebrain. There exists an overlap region 348 between the luminal portion222 of the catheter 200 and the working lumen of the guide sheath 400upon extension of the luminal portion 222 into the target anatomy. Aseal to fluid being injected or aspirated can be achieved within theoverlap region 348 where the OD of the catheter 200 along at least aportion of the distal luminal portion 222 substantially matches theinner diameter of the guide sheath 400 or the difference can be between0.001″-0.002″. The difference between the catheter OD and the innerdiameter of the guide sheath 400 can vary, for example, between 1-2thousandths of an inch, or between 1-4 thousandths of an inch, orbetween 1-12 thousandths of an inch. This difference in OD/ID betweenthe sheath and the catheter can be along the entire length of the distalluminal portion 222 or can be a difference in a discrete region of thedistal luminal portion 222, for example, a cylindrical, proximal endregion of the distal luminal portion 222. In some implementations, aseal to fluid being injected or aspirated between the catheter and thesheath can be achieved within the overlap 348 between theirsubstantially similar dimensions without incorporating any separatesealing structure or seal feature. In some implementations, anadditional sealing structure located near the proximal end region of thedistal luminal portion 222 provides sealing between the inner diameterof the sheath and the outer diameter of the catheter.

The length of the overlap region 348 between the sheath and the distalluminal portion varies depending on the distance between the distal endof the sheath and the embolus as well as the length of the luminalportion 222 between its proximal and distal ends. The overlap region 348can be sized and configured to create a seal that allows for acontinuous aspiration lumen from the distal tip region of the catheter200 to a proximal end region 403 of the guide sheath 400 where it can beconnected to an aspiration source. In some implementations, the strengthof the seal achieved can be a function of the difference between theouter diameter of the catheter 200 and the inner diameter of the workinglumen as well as the length of the overlap region 348, the force of thesuction applied, and the materials of the components. For example, thesealing can be improved by increasing the length of the overlap region348. However, increasing the length of the overlap region 348 can resultin a greater length through which aspiration is pulled through thesmaller diameter of the luminal portion 222 rather than the largerdiameter of the working lumen. As another example, higher suction forcesapplied by the aspiration source can create a stronger seal between theluminal portion 222 and the working lumen even in the presence of ashorter overlap region 348. Further, a relatively softer materialforming the luminal portion and/or the body 402 can still provide asufficient seal even if the suction forces are less and the overlapregion 348 is shorter. In an implementation, the clearance of theoverlap region 348 can enable sealing against a vacuum of up toapproximately 28 inHg with minimal to no leakage. The clearance of theoverlap region can enable sealing against a vacuum of up to about 730mmHg with minimal to no leakage.

In other implementations, the overlap region 348 itself does not providethe sealing between the body 402 and the luminal portion 222. Rather, anadditional sealing element positioned within the overlap region 348, forexample, a discreet location along a region of the luminal portion 222narrows the gap between their respective ID and ODs such that sealing isprovided by the sealing element within the overlap region 348. In thisimplementation, the location of the seal between the luminal portion 222and the body 402 can be positioned more proximally relative to certaintortuous regions of the anatomy. For example, the proximal end region ofthe luminal portion 222 can have a discreet step-up in outer diameterthat narrows the gap between the OD of the luminal portion 222 and theID of the body 402. This step-up in outer diameter of the luminalportion 222 can be positioned relative to the overall length of theluminal portion 222 such that the sealing region between the twocomponents avoids making sharp turns. For example, the sealing regioncan include the proximal end region of the luminal portion 222 a certaindistance away from the distal tip of the catheter and this sealingregion can be designed to remain within the descending aorta DA when thedistal end region of the luminal portion 222 is advanced through theaortic arch, into the brachiocephalic trunk BT, the right common carotidRCC, up to the level of the petrous portion of the internal carotidartery and beyond. Maintaining the sealing region below the level of theaortic arch while the distal end of the catheter is positioned within,for example, the M1 region of the MCA is a function of the length of theluminal portion 222 as well as the length and position of the sealingportion on the catheter. The sealing region on the luminal portion 222can be located a distance from the distal tip of the catheter that is atleast about 40 cm, 45 cm, 50 cm, 55 cm, 60 cm, 65 cm, 70 cm, up to about75 cm from the distal tip of the catheter.

Use of the term “seal” in the context of the catheter and the guidesheath refers to a condition where upon application of an aspirationforce fluid is prevented from substantially passing from one side of theseal to the other. For example, the low clearance between the OD of thecatheter and the ID of the sheath at the seal can prevent, uponapplication of aspiration pressure through the system, substantialpassage of blood between outer surface of the catheter and the innersurface of the sheath and thereby create a seal. The seal does notnecessarily mean the entire catheter system is sealed. For example, evenwhen the catheter is “sealed” with the sheath, blood can still beaspirated into the lumen of the catheter and through the guide sheath(at least until “corking” of the distal end of the catheter 200 where afull seal of the entire system may occur).

The brachiocephalic take-off (BT) is typically a very severe turn offthe aortic arch AA for a transfemorally-delivered catheter seeking theright-sided cerebral circulation (shown in FIG. 1C). A cathetertraversing from the femoral artery through the iliac circulation intothe descending aorta DA turns as it approaches the aortic arch AA andreaches across the take-off of other great vessels to reach thebrachiocephalic take-off (BT), which is the furthest “reach” of thegreat vessels of the aortic arch AA. FIG. 1C shows the substantial andobligatory S-turn created by that anatomy. A catheter must traverse thisS-turn along a path of insertion from a femoral artery insertionlocation in order to reach the internal carotid artery (ICA). The leftICA often takes off from the brachiocephalic and thus, has a similarchallenge and can create an even tighter S-turn. Should the left ICAhave a typical take-off between the brachiocephalic BT and the leftsubclavian artery LSA take-off, then the reach may be less severe, butan S-turn still develops of lesser severity. In some implementations,the length of the luminal portion 222 is sufficient to reach a region ofthe M1 segment of the middle cerebral artery (MCA) and other majorvessels from a region of the internal carotid artery while the proximalend region of the luminal portion 222 of the catheter 200 is stillmaintained proximal to certain tortuous anatomies (e.g. brachiocephalictake-off BT, the aortic arch AA, or within the descending aorta DA). Inan implementation, the luminal portion 222 of the catheter has a lengthsufficient to position its distal end within the M1 segment of the MCAand a proximal end within the aortic arch proximal to take-offs from thearch. In an implementation, the luminal portion 222 of the catheter hasa length sufficient to position its distal end within the M1 segment ofthe MCA and a proximal end within the descending aorta DA proximal tothe aortic arch AA. Used in conjunction with a guide sheath 400 having asheath body 402 and a working lumen, in an implementation where thecatheter 200 reaches the ICA and the distance to embolus can be lessthan 20 cm.

The catheter 200 can telescope relative to the sheath (and/or relativeto another catheter 200) such that the distal end of the distal luminalportion 222 can reach cerebrovascular targets within, for example, theM1, M2 regions while the proximal end of the distal luminal portion 222remains proximal to or below the level of severe turns along the path ofinsertion. For example, the entry location of the catheter system can bein the femoral artery and the target embolus can be distal to the rightcommon carotid artery (RCC), such as within the M1 segment of the middlecerebral artery on the right side. The proximal end region of the distalluminal portion 222 (e.g. where the sealing element is located and/orwhere the material transition to the proximal extension 230 occurs) canremain within a vessel that is proximal to severely tortuous anatomy:the carotid siphon, the right common carotid RCC, the brachiocephalictrunk BT, the take-off of the brachiocephalic artery from the aorticarch, the aortic arch AA as it transitions from the descending aorta DA.The descending aorta DA is a consistently straight segment in mostanatomies. FIG. 1C illustrates the aortic arch AA, which separates theascending aorta AscA and descending aorta DA. The distal-most carotidfrom a femoral access point is the right common carotid RCC artery,which takes off from the brachiocephalic trunk BT (or the left commoncarotid LCC, which takes off from the same brachiocephalic trunk BT insome patients—the so-called “bovine anatomy”). The distal luminalportion 222 may have a length that, when inserted into the RCC, isconfigured to extend from a target location in the M1 or M2 regions downto the brachiocephalic trunk BT, or down to the level of the aortic archAA, or down to the descending aorta DA, which is sometimes referred toherein as being “below the takeoff” of the brachiocephalic trunk BT.This avoids inserting the stiffer proximal extension 230, or thematerial transition between the stiffer proximal extension 230 and thedistal luminal portion 222, from taking the turn of the aortic arch orthe turn of the brachiocephalic take-off, which can often be verysevere. The turn of the aortic arch and the takeoff of thebrachiocephalic are often the first severe turns catheters are likely totraverse as they ascend to the brain via the RCC artery. The lessflexible portions of the catheter segment are able to avoid the regionsof increased tortuosity near the level of the internal carotid artery.The distal luminal portion 222 can transition in flexibility towards theproximal region to approach the flexibility of the stiffer proximalextension 230. The distal end of the catheter can be used to target theleft cerebral circulation while the proximal extension 230 of thecatheter 200 as well as the material transitions of the distal luminalportion 222 near the proximal extension 230 remain below the level oftortuosity of the brachiocephalic turn (e.g., within the aorta, proximalto the take-off of the left common carotid (LCC) artery, and preferablywithin the descending aorta DA). Similarly, the sealing region or amajority of the sealing region between the distal luminal portion 222and the sheath preferably remains proximal to these severe turns.

In some implementations, the distal luminal portion 222 can have alength that allows the distal end of the distal luminal portion 222 toreach distal to the carotid siphon into the cerebral portion of theinternal carotid artery while at the same time the proximal end of thedistal luminal portion 222 (e.g. where it transitions to the proximalextension 230 as will be described in more detail below) remains withinthe aorta proximal to the take-off of the brachiocephalic trunk BT, forexample within the descending aorta DA (see FIG. 2C). In thisimplementation, the distal luminal portion can be between about 35 cmand 75 cm in length, for example, between 45 cm-70 cm, or 65 cm long.

The attachment region between the more rigid, proximal extension 230 andthe more flexible, distal luminal portion 222 creates a transition inmaterial and flexibility that can be prone to kinking. Thus, it ispreferable to avoid advancing the attachment region into extremecurvatures. For example, the distal luminal portion 222 can have alength that allows the point of attachment to be advanced no furtherthan the first turn of the carotid siphon, or no further than thebrachiocephalic artery take-off, or nor further than the aortic arch AA,or no further than the descending aorta DA when the catheter is advancedfrom a femoral access site. In some implementations, the distal luminalportion 222 has a length sufficient to allow the point of attachment toremain within the descending aorta DA while still accessing M1 or M2regions of the neurovasculature. Locating the material transition withinthe extreme turn of the brachiocephalic take-off BT from the aortic archAA is generally avoided when the distal luminal portion 222 has a lengththat is between about 35 cm to about 75 cm, or 45 cm-70 cm, or 65 cm.

The site of insertion for the guide sheath 400 and thus for the catheter200 being inserted through the guide sheath 400 can vary including thefemoral artery near the groin as well as the carotid, radial, ulnar, orbrachial arteries of the arm, or subclavian artery. The length of thedistal luminal portion 222 can remain substantially the same no matterthe point of access being used to ensure the distal end of the distalluminal portion 222 is long enough to reach the distal regions of the M1or M2 while the material transition with the proximal extension 230remains proximal to the brachiocephalic take-off (e.g., within theaortic arch). The length of the proximal extension 230, however, may beshorter for certain access points such as the subclavian artery comparedto a catheter designed for insertion from more distant access pointssuch as the femoral artery. Similar modifications can be made to theguide sheath 400 and the catheter advancement element 300 if accesspoints other than the femoral artery are used. Alternatively, thecatheter lengths can remain unchanged regardless the access point beingused.

In some implementations, the distal luminal portion 222 can have alength that allows the distal end of the distal luminal portion 222 toreach distal to the carotid siphon into the cerebral portion of theinternal carotid artery while at the same time the proximal end of thedistal luminal portion 222 (e.g. where it transitions to the proximalextension 230 as will be described in more detail below) remains withinthe aorta proximal to the take-off of the brachiocephalic trunk BT, forexample within the descending aorta DA (see FIG. 1C). In thisimplementation, the distal luminal portion can be between about 35 cmand 60 cm.

As mentioned, the point of attachment between the proximal extension 230and the distal luminal portion 222 creates a transition in material andflexibility that can be prone to kinking. Thus, it is preferable toavoid advancing the point of attachment into extreme curvatures. Forexample, the distal luminal portion 222 can have a length that allowsthe point of attachment to be advanced no further than the first turn ofthe carotid siphon, or no further than the brachiocephalic arterytake-off BT, or the aortic arch AA. In some implementations, the distalluminal portion 222 has a length sufficient to allow the point ofattachment to remain within the descending aorta DA while stillaccessing M1 or M2 regions of the neurovasculature. Locating thematerial transition within the extreme turn of the brachiocephalictake-off BT from the aortic arch AA is generally avoided when the distalluminal portion 222 has a length that is between about 35 cm to about 60cm.

As described above, a seal can be created at the overlap region 348between the distal luminal portion 222 and the sheath body 402. It canbe generally desirable to position the sealing overlap region 348outside of extreme curvatures of the neurovasculature. In someimplementations, the distal luminal portion 222 can have a length thatallows for the distal end of the distal luminal portion 222 to extenddistal to the carotid siphon into the cerebral portion of the internalcarotid artery while at the same time the overlap region 348 remainproximal to the brachiocephalic takeoff BT, the aortic arch AA, orwithin the descending aorta DA. In this implementation, the length canbe between about 35 cm to about 60 cm, about 40 cm to about 60 cm, orgreater than 40 cm up to less than the working length of the sheath body402.

As described above with respect to FIG. 2C, the unreinforced region 407of the distal tip 406 of the sheath 400 can have a length that allows itto provide sufficient sealing force onto the outer surface of thecatheter 200 upon application of a negative pressure. The distal luminalportion 222 of the catheter 200 used with this implementation of sheath400 can have a length that is shorter than 60 cm, shorter than 50 cm,shorter than 40 cm, shorter than 35 cm, shorter than 30 cm to about 10cm. For example, the distal luminal portion 222 of the catheter 200 whenused with a sheath 400 having an unreinforced region 407 configured forsealing can be less than about 30 cm, for example, between 10 cm andabout 30 cm.

Sealing within the overlap region 348 can be due to the small differencein inner and outer diameters. The proximal end region of the distalluminal portion 222 can have a step-up in outer diameter (e.g. increasedwall thickness) providing a region of localized sealing with the innerdiameter of the guide sheath. Additionally or alternatively, thelocalized sealing can be due to an additional sealing element positionedon an external surface of the distal luminal portion or an inner surfaceof the sheath body. A sealing element can include a stepped up diameteror protruding feature in the overlap region. The sealing element caninclude one or more external ridge features. The one or more ridgefeatures can be compressible when the luminal portion is inserted intothe lumen of the sheath body. The ridge geometry can be such that thesealing element behaves as an O-ring, quad ring, or other piston sealdesign. The sealing element can include one or more inclined surfacesbiased against an inner surface of the sheath body lumen. The sealingelement can include one or more expandable members actuated to seal. Theinflatable or expandable member can be a balloon or covered braidstructure that can be inflated or expanded and provide sealing betweenthe two devices at any time, including after the catheter is positionedat the desired site. Thus, no sealing force need be exerted on thecatheter during positioning, but rather applied or actuated to sealafter the catheter is positioned. The sealing element can be positionedon the external surface of the distal luminal portion, for example, nearthe proximal end region of the distal luminal portion and may be locatedwithin the overlap region. More than a single sealing element can bepositioned on a length of the catheter.

In some implementations, the additional sealing element of the distalluminal portion 222 can be a cup seal, a balloon seal, or a disc sealformed of a soft polymer positioned around the exterior of the distalluminal portion near the overlap region to provide additional sealing.The sealing element can be a thin-wall tubing with an outer diameterthat substantially matches the inner diameter of the sheath body lumen.The tubing can be sealed on one end to create a cup seal or on both endsto create a disc or balloon seal. The balloon seal can include trappedair that creates a collapsible space. One or more slits can be formedthrough the wall tubing such that the balloon seal can be collapsibleand more easily passed through an RHV. The balloon seal need not includeslits for a less collapsible sealing element that maintains the trappedair. The sealing element can be tunable for sheath fit and collapseachieved.

In some implementations, the system can include one or more featuresthat restrict extension of the catheter 200 relative to the sheath 400to a particular distance such that the overlap region 348 achieved isoptimum and/or the catheter 200 is prevented from being over-inserted.For example, a tab can be positioned on a region of the catheter 200such that upon insertion of the catheter 200 through the sheath 400 aselected distance, the tab has a size configured to abut against theport through which the catheter 200 is inserted to prevent furtherdistal extension of the catheter 200 through the sheath 400. A tab canalso be positioned on a region of the catheter advancement element 300to ensure optimum extension of the catheter advancement element 300relative to the distal end of the catheter 200 to aid in advancement ofthe catheter 200 into the intracranial vessels.

Again with respect to FIG. 3, the proximal extension 230 is configuredto move the distal luminal portion 222 in a bidirectional manner throughthe working lumen of the guide sheath 400 such that the distal luminalportion 222 can be advanced out of the guide sheath 400 into a targetlocation for treatment within the target vessel. In some implementationsand as shown in FIG. 3, the proximal extension 230 of the catheter 200can have a smaller outer diameter than the outer diameter of the distalluminal portion 222 forming a proximal spine or tether to the catheter200. A smaller outer diameter for the proximal extension 230 than theouter diameter of the distal luminal portion 222 allows for the largerdiameter working lumen of the sheath 400 to maintain greater aspirationforces than would otherwise be provided by the smaller diameter luminalportion 222 of the catheter 200 or allow for the delivery of workingdevices through the lumen with less frictional forces. The markedlyshorter length of the luminal portion 222 results in a step up inluminal diameter between the luminal portion 222 contiguous with theworking lumen providing a markedly increased radius and luminal area fordelivery of a working device and/or aspiration of the clot, particularlyin comparison to other systems where the aspiration lumen runs along theentire inner diameter of the aspiration catheter. More particularly, thecombined volume of the luminal area of the catheter 200 and the luminalarea of the working lumen proximal to the distal luminal portion 222 isgreater than the luminal area of the large bore catheter along theentire length of the system. Thus, the likelihood of removing theembolus during a single aspiration attempt may be increased. Moreparticularly, the stepped up luminal diameter along the proximalextension 230 may enable a greater aspiration force to be achievedresulting in improved aspiration of the embolus. Further, thisconfiguration of the catheter 200 and proximal extension 230 greatlyspeeds up the time required to retract and re-advance the catheter 200and/or working devices through the working lumen out the distal lumen408. This describes the time it takes to aspirate the occlusion. Theproximal extension 230 of the catheter 200 has a length and structurethat extends through the working lumen of the sheath-guide 400 to aproximal end of the system 100 such that the proximal extension 230 canbe used to advance and retract the catheter 200 through the workinglumen. The proximal extension 230 of the catheter 200, however, takes uponly a fraction of the luminal space of the system 100 resulting inincreased luminal area for aspiration and/or delivery of workingdevices. The stepped up luminal diameter also increases the annular areaavailable for forward flushing of contrast, saline, or other solutionswhile devices such as microcatheters or other devices may be coaxiallypositioned in the luminal portion 222 of the catheter 200 and/or theworking lumen. This can increase the ease and ability to performangiograms during device navigation.

In an implementation, the distal luminal portion 222 of the catheter 200is constructed to be flexible and lubricious, so as to be able to safelynavigate to the target location. The distal luminal portion 222 can bekink resistant and collapse resistant when subjected to high aspirationforces so as to be able to effectively aspirate a clot. The luminalportion 222 can have increasing flexibility towards the distal end withsmooth material transitions along its length to prevent any kinks,angulations or sharp bends in its structure, for example, duringnavigation of severe angulations such as those having 90° or greater to180° turns, for example at the aorto-iliac junction, the left subclaviantake-off from the aorta, the takeoff of the brachiocephalic (innominate)artery from the ascending aorta and many other peripheral locations justas in the carotid siphon. The distal luminal portion 222 can transitionfrom being less flexible near its junction with the proximal extension230 to being more flexible at the distal-most end. The change inflexibility from proximal to distal end of the distal luminal portion222 can be achieved by any of a variety of methods as described herein.For example, a first portion of the distal luminal portion 222 can beformed of a material having a hardness of at least about 72 D or greateralong a first length, a second portion can be formed of a materialhaving a hardness that is less than about 72 D, such as about 55 D alonga second length, a third portion can be formed of a material having ahardness that is less than about 55 D, such as about 40 D along a thirdlength, a fourth portion can be formed of a material having a hardnessless than about 40 D, such as about 35 D along a fourth length, a fifthportion can be formed of a material having a hardness less than about 35D, such as about 25 D along a fifth length, a sixth portion can beformed of a material having a hardness less than about 25 D, such asabout 85 A Tecoflex along a sixth length, a seventh portion can beformed of a material having a hardness less than about 85 A, such asabout 80 A Tecoflex. In some implementations, the final distal portionof the distal luminal portion 222 of the catheter 200 can be formed of amaterial such as Tecothane having a hardness of 62 A that is matched inhardness to a region of the catheter advancement element 300, which willbe described in more detail below. Thus, the distal luminal portion 222transitions from being less flexible near its junction with the proximalextension 230 to being more flexible at the distal-most end where, forexample, a distal tip of the catheter advancement element 300 can extendfrom. Other procedural catheters described herein can have a similarconstruction providing a variable relative stiffness that transitionsfrom the proximal end towards the distal end of the catheter as will bedescribed elsewhere herein.

The material hardnesses described herein with respect to the distalluminal portion 222 of the catheter as well as with regard to theflexible elongate body 360 of the catheter advancement element 300 canbe achieved by a single polymer material or by mixtures of polymermaterials. For example, a mixture of 35 D PEBAX and 55 D PEBAX canprovide a harder polymeric material than that of 35 D PEBAX alone and asofter polymer material than that of 55 D PEBAX alone. The polymersegments of the various catheter components described herein canincorporate any of a variety of hardnesses between the specifichardnesses identified by blending of one or more polymer materials toachieve a transition in flexibility along a length of the structure.Additionally, the ranges of hardnesses between the proximal end portionsof the catheters described herein and a distal end portions of thecatheters can vary from greater than 72 D PEBAX (e.g. 72 D PEBAXreinforced with a metallic or non-metallic element) down to less than 35D (e.g., 62 A Tecothane).

The distal luminal portion 222 can include two or more layers. In someimplementations, the distal luminal portion 222 includes an innerlubricious liner, a reinforcement layer, and an outer jacket layer, eachof which will be described in more detail.

The lubricious inner liner can be a PTFE liner, with one or morethicknesses along variable sections of flexibility. The PTFE liner canbe a tubular liner formed by dip coating or film-casting a removablemandrel, such as a silver-plated copper wire as is known in the art.Various layers can be applied having different thicknesses. For example,a base layer of etched PTFE can be formed having a thickness of about0.005″. A second, middle layer can be formed over the base layer that isTecoflex SG-80A having a thickness of about 0.0004″. A third, top layercan be formed over the middle layer that is Tecoflex SG-93A having athickness of about 0.0001″ or less. The distal luminal portion 222 canadditionally incorporate one or more reinforcement fibers (see FIGS.8B-8C) configured to prevent elongation of the coils, as will bedescribed in more detail below. A reinforcement layer and/orreinforcement fiber can be applied to the inner liner, followed by theouter jacket layer and/or additional outer coating prior to removing themandrel by axial elongation.

The reinforcement layer is a generally tubular structure formed of, forexample, a wound ribbon or wire coil or braid. The material for thereinforcement structure may be stainless steel, for example 304stainless steel, Nitinol, cobalt chromium alloy, or other metal alloythat provides the desired combination of strengths, flexibility, andresistance to crush. In some implementations, the distal luminal portion222 has a reinforcement structure that is a Nitinol ribbon wrapped intoa coil. For example, the coil reinforcement can be a tapered ribbon ofNitinol set to a particular inner diameter (e.g. 0.078″ to 0.085″ innerdiameter) and having a pitch (e.g. between 0.012″ and 0.016″). Theribbon can be 304 stainless steel (e.g. about 0.012″×0.020″). The coilcan be heat-set prior to transferring the coil onto the catheter. Thepitch of the coil can increase from proximal end towards distal end ofthe distal luminal portion 222. For example, the ribbon coils can havegaps in between them and the size of the gaps can increase movingtowards the distal end of the distal luminal portion 222. For example,the size of the gap between the ribbon coils can be approximately 0.016″gap near the proximal end of the distal luminal portion 222 and the sizeof the gap between the ribbon coils near the distal end can be largersuch as 0.036″ gap. This change in pitch provides for increasingflexibility near the distal-most end of the distal luminal portion 222.The reinforcement structure can include multiple materials and/ordesigns, again to vary the flexibility along the length of the distalluminal portion 222.

The outer jacket layer may be composed of discreet sections of polymerwith different durometers, composition, and/or thickness to vary theflexibility along the length of the distal luminal portion 222 asdescribed above.

At least a portion of the outer surface of the catheter 200 can becoated with a lubricious coating such as a hydrophilic coating. In someimplementations, the coating may be on an inner surface and/or an outersurface to reduce friction during tracking. The coating may include avariety of materials as is known in the art. The proximal extension 230may also be coated to improve tracking through the working lumen.Suitable lubricious polymers are well known in the art and may includesilicone and the like, hydrophilic polymers such as high-densitypolyethylene (HDPE), polytetrafluoroethylene (PTFE), polyarylene oxides,polyvinylpyrolidones, polyvinyl alcohols, hydroxy alkyl cellulosics,algins, saccharides, caprolactones, HYDAK coatings (e.g. B-23K,HydroSleek), and the like, and mixtures and combinations thereof.Hydrophilic polymers may be blended among themselves or with formulatedamounts of water insoluble compounds (including some polymers) to yieldcoatings with suitable lubricity, bonding, and solubility.

In an implementation, the distal-most end of the distal luminal portion222 has a flexural stiffness (E*I) in the range of 0.05-0.5 N-mm² andthe remaining portion of the distal luminal portion 222 has a higherflexural stiffness, where E is the elastic modulus and I is the areamoment of inertia of the device. These bending stiffness ranges in N-mm²can be measured by assessing the force in Newtons generated upondeflecting the device a certain distance using a particular gaugelength. The bending stiffness (Elastic modulus×area moment of inertia)can be calculated according to the equation EI=FL³/3δ, where F isdeflection force, L is gauge length, and δ is deflection. For example,using a 3 mm gauge length (L=3 mm) and deflecting a tip of the catheter2 mm (δ=2 mm), 0.05-0.5 N of force can be generated. In someimplementations, the distal-most end of the distal luminal portion 222can range in bending stiffness between 0.225-2.25 N-mm². As acomparison, the flexibility of the catheter advancement element 300based on similar deflection measurements and calculations can be asfollows. Upon 2 mm deflection and force gauge length of 3 mm, thecatheter advancement element 300 can range in bending force between0.005-0.05 Newtons or can range in bending stiffness between0.0225-0.225 N-mm². Other procedural catheters described herein can havea similar flexibility ranges providing a variable relative stiffnessthat transitions from the proximal end towards the distal end of thecatheter as will be described elsewhere herein and as also described inU.S. Publication No. 2019/0351182, filed May 16, 2019, which isincorporated by reference herein in its entirety.

The catheter 200 can reach anatomic targets with the largest possibleinternal lumen size for the catheter with the help of the exceedinglyflexible catheter advancement element 300. Both the catheter 200 and thecatheter advancement element 300, individually and assembled as asystem, are configured to navigate around a 180° bend around a radius assmall as 0.050″ to 0.150″ or as small as 0.080″ to 0.120″ withoutkinking, for example, to navigate easily through the carotid siphon. Thecatheter 200 and catheter advancement element 300 can resist kinking andovalizing even while navigating a tortuous anatomy up to 180°×0.080″radius bend.

In some implementations, the distal luminal portion 222 includes two ormore layers. In some implementations, the distal luminal portion 222includes an inner lubricious liner, a reinforcement layer, and an outerjacket layer. The outer jacket layer may be composed of discreetsections of polymer with different durometers, composition, and/orthickness to vary the flexibility along the length of the distal luminalportion 222. In an implementation, the lubricious inner liner is a PTFEliner, with one or more thicknesses along variable sections offlexibility. In an implementation, the reinforcement layer is agenerally tubular structure formed of, for example, a wound ribbon orwire coil or braid. The material for the reinforcement structure may bestainless steel, for example 304 stainless steel, nitinol, cobaltchromium alloy, or other metal alloy that provides the desiredcombination of strengths, flexibility, and resistance to crush. In animplementation, the reinforcement structure includes multiple materialsand/or designs, again to vary the flexibility along the length of thedistal luminal portion 222. In an implementation, the outer surface ofthe catheter 200 is coated with a lubricious coating such as ahydrophilic coating. The proximal control element 230 may also be coatedto improve tracking through the working lumen. Suitable lubriciouspolymers are well known in the art and may include silicone and thelike, hydrophilic polymers such as high-density polyethylene (HDPE),polytetrafluoroethylene (PTFE), polyarylene oxides,polyvinylpyrolidones, polyvinyl alcohols, hydroxy alkyl cellulosics,algins, saccharides, caprolactones, and the like, and mixtures andcombinations thereof.

Again with respect to FIGS. 2A-2B, the distal luminal portion 222 of thecatheter 200 can have a plurality of radiopaque markers. A firstradiopaque marker 224 a can be located near the distal tip region to aidin navigation and proper positioning of the tip under fluoroscopy.Additionally, a proximal region of the catheter 200 may have one or moreproximal radiopaque markers 224 b so that the overlap region 348 can bevisualized as the relationship between a radiopaque marker 411 on theguide sheath 400 and the radiopaque marker 224 b on the catheter 200.The proximal region of the catheter 200 may also have one or moreradiopaque markings providing visualization, for example, of theproximal opening into the single lumen of the catheter as will bedescribed in more detail below. In an implementation, the two radiopaquemarkers (marker 224 a at distal tip and a more proximal marker 224 b)are distinct so as to minimize confusion of the fluoroscopic image, forexample the catheter proximal marker 224 b may be a single band and themarker 411 on the guide sheath 400 may be a double band and any markerson a working device delivered through the distal access system can haveanother type of band or mark. The radiopaque markers 224 of the distalluminal portion 222, particularly those near the distal tip regionnavigating extremely tortuous anatomy, can be relatively flexible suchthat they do not affect the overall flexibility of the distal luminalportion 222 near the distal tip region. The radiopaque markers 224 canbe tungsten-loaded or platinum-loaded markers that are relativelyflexible compared to other types of radiopaque markers used in deviceswhere flexibility is not paramount. In some implementations, theradiopaque marker can be a band of tungsten-loaded PEBAX having adurometer of 35 D.

As best shown in FIGS. 8B-8C, at least one reinforcement fiber 801 canbe incorporated within a wall of the distal luminal portion 222 toprevent elongation of a coiled reinforcement layer 803. The fiber 801can be positioned between the liner layer 805 and the reinforcementlayer 803. The fiber 801 can extend along the longitudinal axis A of thecatheter 200 from a proximal end region of the distal luminal portion222 to a distal end region of the portion 222. The proximal end of thefiber 801 can be coupled to a region of the distal luminal portion 222near where it couples to the proximal extension 230. A distal end of thefiber 801 can terminate near the distal end of the distal luminalportion 222. The distal end of the fiber 801 can be captured between thedistal marker band 224 a and an end of the reinforcement layer 803. Thedistal marker band 224 a can be fully encapsulated between the innerliner 805 and the outer jacket 807. In some implementations, the distalend of the fiber 801 extends distal to the last coil of thereinforcement layer 803 running under the marker band 224 a and thenlooping around the band 224 a back in a proximal direction. The free endof the fiber 801 is thereby captured under the reinforcement layer 803and the marker band 224 a. The reinforcement fiber 801 thus terminatesat the location the reinforcement layer 803 terminates thereby leaving alength of between about 10 cm-12 cm of the unreinforced distal-most tipregion. The catheter 200 can include a plurality of reinforcement fibers801 extending longitudinally along the distal luminal portion 222, suchas two, three, four, or more fibers 801 distributed around thecircumference of the portion 222 and aligned parallel with one anotherand with the longitudinal axis A of the catheter 200. The reinforcementfiber 801 may also terminate at a more distal location or at a moreproximal location than the location of the distal terminal marker 224 a.The material of the reinforcement fiber 801 can vary, including but notlimited to various high tenacity polymers like polyester, PEEK, andother similar materials.

The distal luminal portion 222 of the catheter 200 can have a proximalextension 230 coupled near a proximal opening into the single lumen ofthe distal luminal portion 222. The distal luminal portion 222 and theproximal extension 230 can be attached to one another by a coupling band901 (see FIGS. 9A-9C). A proximal end 905 of the coupling band 901 canattach to a distal end of the proximal extension 230 and a distal end ofthe coupling band 901 can attach to the distal luminal portion 222. Theproximal end 905 of the coupling band 901 may include a slot 907configured to be welded with the proximal extension 230 of the catheter200. The catheter 200 may include a strain relief along a skive lengthsuch as a tungsten loaded PEBAX. The distal end of the coupling band 901can be cut to form a plurality of spirals 903. These spirals 903 areconfigured to intersperse with the coils of the reinforcement layer 803at the proximal end region of the distal luminal portion 222. The sizeof the gap between the spirals 903 of the coupling band 901 can besubstantially similar to the size of the gap between the coils of thereinforcement layer 803 such that they can neatly intersperse with oneanother without creating any localized areas of increased wall thicknessdue to overlap. The thickness of the spirals 903 can, but need not, besimilar to the thickness of the ribbon forming the reinforcement layer803. For example, the coiled reinforcement layer 803 can be formed of aNitinol ribbon having a thickness of about 0.003″. The coupling band 901can have a wall thickness that is about 0.003″ such that the spirals 903and the coils of the reinforcement layer 803 can be similar in materialthickness. This similarity in material thickness between the coils andthe spirals 903 contribute to a generally uniform outer profile that canbe kept to a minimum and avoid creating a substantially increased wallthickness in this coupling region. A low profile proximal end of thedistal luminal portion 222 aids in maximizing the inner diameter whilekeeping the outer diameter as small as possible, for example, such thatthe inner diameter of the guide sheath to a minimum (e.g. less thanabout 0.113″ or about 0.107″). The coupling band 901 can include anaperture 911 through middle region 909 that is configured to receive aproximal end of the reinforcement fiber 801 extending longitudinallythrough the distal luminal portion 222. The region of overlap betweenthe distal end of the proximal control element and the distal luminalportion 222 can vary, but can be at least about 5 mm, at least about 7mm, at least about 10 mm to provide a smooth and even transition. Theoverlap between the proximal control element and the distal luminalportion 222 may be about 5 mm up to about 15 mm.

As mentioned the distal end of the proximal extension 230 can be weldedto the proximal end 905 of the coupling band 901. In someimplementations, the distal end region of the proximal extension 230 isskived in places and is flat in other places. The proximal extension 230can be a stainless steel ribbon (e.g. 0.012″×0.020″ or 0.014″×0.020″along a majority of its length). A distal end region of the proximalextension 230 can have a discontinuous taper that allows for thethickness of the ribbon to transition from the thickness of 0.012″ or0.014″ down to a thickness that matches or is not significantlydifferent from a thickness of the spirals 903 on the coupling band 901that is attached to a proximal end region of the distal luminal portion222. The discontinuous taper can include a flat length bound on proximaland distal ends by a tapered length. The flat length allows for a moreuniform, minimum material thickness between the distal luminal portion222 and the proximal extension 230 that avoids introducing weak pointsthat are more prone to kinking. For example, the distal end region ofthe proximal extension 230 can have a first tapered length thattransitions in thickness from 0.012″ to a thickness of 0.008″ and asecond tapered length that transitions from the flat length thicknessdown to about 0.003″. In other implementations, the distal end region ofthe proximal extension 230 can have a first tapered length thattransitions in thickness from 0.014″ to a thickness of 0.010″ and asecond tapered length that transitions from the flat length thicknessdown to about 0.003″. The spirals 903 of the coupling band 901 can havea thickness matches this terminal thickness of the proximal extension230. The lengths of the tapered and flat portions can vary. In someimplementations, the first tapered length can be approximately 0.12 cm,the flat length can be approximately 0.2 cm, and the second taperedlength can be approximately 0.15 cm. The uniform thickness along thisflat length provides for a useful target in terms of manufacturing thecatheter. The catheter need not incorporate a ribbon proximal extension230 and can have any of a variety of configuration as describedelsewhere herein.

As mentioned previously, the proximal extension 230 is configured toallow distal advancement and proximal retraction of the catheter 200through the working lumen of the guide sheath 400 including passage outthe distal lumen 408. In an implementation, the length of the proximalextension 230 is longer than the entire length of the guide sheath 400(from distal tip to proximal valve), such as by about 5 cm to 15 cm. Thelength of the body 402 can be in the range of 80 to 90 cm or up to about100 cm or up to about 105 cm and the length of the proximal extension230 can be between 90-100 cm.

Again with respect to FIG. 3, the proximal extension 230 can include oneor more markers 232 to indicate the overlap between the distal luminalportion 222 of the catheter 200 and the sheath body 402 as well as theoverlap between the distal luminal portion 222 of the catheter 200 andother interventional devices that may extend through the distal luminalportion 222. At least a first mark 232 a can be an RHV proximity markerpositioned so that when the mark 232 a is aligned with the sheathproximal hemostasis valve 434 during insertion of the catheter 200through the guide sheath 400, the catheter 200 is positioned at thedistal-most position with the minimal overlap length needed to createthe seal between the catheter 200 and the working lumen. At least asecond mark 232 b can be a Fluoro-saver marker that can be positioned onthe proximal extension 230 and located a distance away from the distaltip of the distal luminal portion 222. In some implementations, a mark232 can be positioned about 100 cm away from the distal tip of thedistal luminal portion 222.

The proximal extension 230 can include a gripping feature such as a tab234 on the proximal end to make the proximal extension 230 easy to graspand advance or retract. The tab 234 can couple with one or more othercomponents of the system as will be described in more detail below. Theproximal tab 234 can be designed to be easily identifiable amongst anyother devices that may be inserted in the sheath proximal valve 434,such as guidewires or retrievable stent device wires. A portion of theproximal extension 230 and/or tab 234 can be colored a bright color, ormarked with a bright color, to make it easily distinguishable fromguidewire, retrievable stent tethers, or the like. Where multiplecatheters 200 are used together in a nesting fashion to reach moredistal locations within the brain, each proximal extension 230 and/ortab 234 can be color-coded or otherwise labeled to clearly show to anoperator which proximal extension 230 of which catheter 200 it iscoupled to. The proximal portion 366 of the catheter advancement element300 can also include a color to distinguish it from the proximalextension 230 of the catheter 200.

The tab 234 can be integrated with or in addition to a proximal hubcoupled to a proximal end of the proximal extension 230. For example, aswill be described in more detail below, the proximal extension 230 canbe a hypotube having a lumen. The lumen of the hypotube can be in fluidcommunication with the proximal hub at a proximal end of the proximalextension 230 such that aspiration forces and/or fluids can be deliveredthrough the hypotube via the proximal hub. The proximal control element230 can also be a solid element and need not include a lumen to directaspiration forces to the distal end of the catheter 200.

The proximal extension 230 can be configured with sufficient stiffnessto allow advancement and retraction of the distal luminal portion 222 ofthe catheter 200, yet also be flexible enough to navigate through thecerebral anatomy as needed without kinking. The configuration of theproximal extension 230 can vary. In some implementations, the proximalextension 230 can be a tubular element having an outer diameter that issubstantially identical to the outer diameter of the distal luminalportion 222 similar to a typical catheter device. In otherimplementations, the outer diameter of the proximal extension 230 issized to avoid taking up too much luminal area in the lumen of the guidesheath 400 as described above.

The proximal extension 230 can be a solid metal wire that is round,rectangular, trapezoid, D-shape, or oval cross-sectional shape (seeFIGS. 4A-4G). The proximal extension 230 can be a flattened ribbon ofwire having a rectangular cross-sectional shape as shown in FIG. 4A. Theflattened ribbon of wire can also have square, rectangular, or othercross-sectional shape. The ribbon of wire can be curved into a circular,oval, c-shape, or quarter circle or other cross-sectional area along anarc. As such, an inner-facing surface of the ribbon can be substantiallyflat and an outer-facing surface of the ribbon (i.e. the surfaceconfigured to abut against an inner diameter of the access sheaththrough which it extends) can be substantially curved (see FIGS. 4F-4G).The curvature of the surface can substantially match the curvature ofthe inner surface of the access sheath. The resulting cross-sectionalshape of such a ribbon can be generally trapezoidal. The overalldimensions of the ribbon can vary depending on its cross-sectional shapeand the size of the distal luminal portion. The 0.054″ sized catheter200 can have a proximal extension 230 that is trapezoidal or D-shaped incross-section. The inner-facing, flat surface can have a width that isapproximately 0.020″ wide and in the case of the trapezoidal-shapedimplementation, the outer-facing, curved surface can extend along an arcthat is approximately 0.030″ long. The 0.070″ sized catheter 200 canhave a proximal extension that is trapezoidal or D-shaped incross-section, and the width of the inner-facing, flat surface isslightly greater, for example, approximately 0.025″ and in the case ofthe trapezoidal-shaped implementation, the outer-facing, curved surfacecan extend along an arc that is approximately 0.040″ long. The 0.088″sized catheter 200 can have a proximal extension that is trapezoidal orD-shaped in cross-section, and the width of the inner-facing, flatsurface is approximately 0.035″ and the outer-facing, curved surface ofthe trapezoidal-shaped implementation can extend along an arc that isapproximately 0.050″ long.

The proximal extension 230 can be a hollow wire having a lumen 235extending through it, such as a hypotube as shown in FIG. 4B. Thehypotube can have an oval or circular shape. In an implementation, theproximal extension 230 is a ribbon of stainless steel having dimensionsof about 0.012″×0.020″. In an implementation, the proximal extension 230is a ribbon of stainless steel having dimensions of about 0.014″×0.020″.In an implementation, the proximal extension 230 is a round wire, withdimensions from 0.014″ to 0.018″. In another implementation, theproximal extension 230 is a ribbon with dimensions ranging from 0.010″to 0.015″ thick, and 0.015″ thick to 0.025″ thick. In an implementation,the proximal extension 230 is a hypotube formed from a flattened ribbonof stiff material rolled into a tubular shape to have a lumen 235 withor without a polymer jacket and/or liner. In some implementations, theproximal extension 230 can be formed of a flattened ribbon of stainlesssteel and rolled into a hypotube such that the proximal extension 230has a wall thickness of about 0.007″, an inner diameter of about 0.004″and an outer diameter of about 0.018″ before the hypotube is modifiedinto an oval cross-sectional shape. The ovalized hypotube can maintainan inner diameter that is at least 0.001″ along at least a firstdimension and an outer diameter that is at least 0.015″ along at least afirst dimension. In an implementation, the proximal extension 230material is a metal such as a stainless steel or Nitinol as well as aplastic such as any of a variety of polymers. In an implementation, theproximal extension 230 is a stainless steel hypotube having an ovalcross-sectional shape (see FIG. 4B). The oval tubular shape can increasethe column strength, pushability and kink resistance of the proximalextension 230 for improved advancement through tortuous anatomy. Thecross-sectional area of an oval hypotube minimizes the impact of thecatheter 200 on movement of other tools through the working lumen of thesheath 400. FIG. 4C illustrates a cross-sectional view of the workinglumen of the sheath 400 having a proximal portion 230 extendingtherethrough. The proximal portion 230 has a rectangular cross-sectionalshape. FIG. 4D illustrates a cross-sectional view of the working lumenhaving an ovalized hypotube proximal portion 230 and a catheteradvancement element 300 extending therethrough. FIG. 4E illustrates thecomparison of surface area between the rectangular-shaped ribbon and theoval hypotube. The oval hypotube has less surface area compared to therectangular-shaped ribbon allowing for a greater flow rate through theworking lumen, for example, during application of aspirating forces. Thematerials, dimensions, and shape of the proximal extension 230 can beselected based on the materials, dimensions, and shape of the distalluminal portion 222. For example, the proximal extension 230 can be arectangular ribbon of 340 stainless steel that is 0.012″×0.020″ and thedistal luminal portion 222 can have an inner diameter of about 0.054″ toabout 0.072″. In a further implementation, the proximal extension 230can be a rectangular ribbon of 340 stainless steel that is 0.014″×0.020″and the distal luminal portion 222 can have an inner diameter of about0.088″. The additional heft of the stainless steel ribbon 230 can beuseful in advancing a larger inner diameter catheter without kinking. Ifthe proximal portion 230 is formed by a hypotube, the hypotube can besolid hypotube without interruptions through its sidewall or canincorporate an interruption or perforation through the sidewall such asa cut in one or more locations.

Now with respect to FIGS. 5A-5F, the junction between the distal luminalportion 222 of the catheter 200 and the proximal extension 230 can beconfigured to allow a smooth transition of flexibility between the twoportions so as not to create a kink or weak point. The smooth transitionat the joint between the distal luminal portion 222 and the proximalextension 230 also allows for smooth passage of devices through thecontiguous inner lumen created by the working lumen of the guide sheath400 and the lumen 223 of the luminal portion 222 of the catheter 200. Inan implementation, the distal luminal portion 222 has a transitionsection 226 near where the luminal portion 222 couples to the proximalextension 230 (see FIG. 5A). The transition section 226 can have anangled cut such that there is no abrupt step transition from the workinglumen of the guide sheath 400 to the inner lumen 223 of the catheter200. The angled cut can be generally planer. In an alternateimplementation, the angled cut is curved or stepped to provide a moregradual transition zone. The proximal end region of the distal luminalportion 222 can be angled in an oblique manner relative to alongitudinal axis of the catheter 200 such that the proximal end andproximal opening into the lumen are at an angle other than 90° to thelongitudinal axis of the catheter 200, for example between approximately0°, 5°, 10°, 15°, 20°, 25°, 30°, 35°, 40°, or 45° up to less than 90°.The proximal end region of the distal luminal portion 222 can also bealigned substantially perpendicular to the longitudinal axis of thecatheter 200 such that the proximal end and proximal opening into thelumen are substantially 90° to the longitudinal axis of the catheter200. Similarly, the distal end region of the distal luminal portion 222can be angled in an oblique manner relative to a longitudinal axis ofthe catheter 200 such that the distal end and distal opening from thelumen 223 are at an angle other than 90° to the longitudinal axis of thecatheter 200, for example between approximately 0°, 5°, 10°, 15°, 20°,25°, 30°, 35°, 40°, or 45° up to less than 90°. The distal end region ofthe distal luminal portion 222 can also be aligned substantiallyperpendicular to the longitudinal axis of the catheter 200 such that thedistal end and distal opening into the lumen are substantially 90° tothe longitudinal axis of the catheter 200.

The proximal extension 230 can be coupled to a proximal end region ofthe catheter 200 and/or may extend along at least a portion of thedistal luminal portion 222 such that the proximal extension 230 couplesto the distal luminal portion 222 a distance away from the proximal end.The proximal extension 230 can be coupled to the distal luminal portion222 by a variety of mechanisms including bonding, welding, gluing,sandwiching, stringing, tethering, or tying one or more componentsmaking up the proximal extension 230 and/or portion 222. The distalluminal portion 222 and the proximal extension 230 may be joined by aweld bond, a mechanical bond, an adhesive bond, or some combinationthereof. In some implementations, the proximal extension 230 and luminalportion 222 are coupled together by sandwiching the proximal extension230 between layers of the distal luminal portion 222. For example, theproximal extension 230 can be a hypotube or rod having a distal end thatis skived, ground or cut such that the distal end can be laminated orotherwise attached to the layers of the catheter portion 222 near aproximal end region. The skive length of the proximal control element230 can be about 7 mm and can incorporate a tungsten loaded Pebax strainrelief along the length. The region of overlap between the distal end ofthe proximal extension 230 and the portion 222 can be at least about 1cm. This type of coupling allows for a smooth and even transition fromthe proximal extension 230 to the luminal portion 222.

Still with respect to FIGS. 5A-5F, the transition section 226 of thedistal luminal portion 222 can open up into a trough 238 extending alength proximal to the transition section 226. In some implementations,the trough 238 has a cross-sectional geometry that is substantiallycurved. For example, the trough 238 can extend along an arc of thelongitudinal axis of the catheter 200 between about 20 to about 90degrees. In some implementations, the trough 238 is curved to create afunnel-shape and aids in loading and reloading a catheter advancementelement 300 into the lumen of the catheter 200. In otherimplementations, the edges of the trough 238 curve such that the trough238 is not substantially flat. The curved shape can vary including atear-drop shape that allows for a smooth transition and betterloading/reloading of the catheter advancement element 300 into the lumenand avoids flat edges that can abut and catch the component as it isinserted. In other implementations, the trough 238 is substantiallyflat. The trough 238 can provide a smooth transition between distalluminal portion 222 and proximal extension 230 when the device is forcedto bend. This can reduce the likelihood of kinking and facilitatepushing against resistance.

The dimensions of the proximal tail 238 can vary. The proximal tail 238shown in FIGS. 5A-5F is relatively wide compared to the width of theproximal control element 230 and, in turn, can have a greater lengthwithout negatively impacting the ability of other devices to insertthrough the proximal opening into the lumen at the transition region226. In other implementations, the proximal tail 238, defined by aregion that is unsupported by the coils of the reinforcement layer 803and located proximal to the coupling band 901, can have a shorterlength. The width of this proximal tail 238 can taper along this shorterlength to a width of the proximal control element 230. The taperedshorter proximal tail 238 can mitigate issues with insertion of toolsinto the proximal opening. Generally speaking, wide proximal tails 238can be longer than proximal tails 238 that taper down to the width ofthe proximal control element 230.

A proximal region of the distal luminal portion 222 can incorporate oneor more markers to provide visualization under fluoro duringloading/reloading of the catheter advancement element 300. For example,the proximal end region can include a region of Pebax (e.g. 35 D) loadedwith tungsten (80%) for radiopacity. In some implementations, theproximal tail 228 and/or the transition section 226 defining theproximal opening into the lumen of the luminal portion 222 can be coatedor embedded with a radiopaque material such that the opening into thelumen can be fully visualized during use. The radiopaque materialembedded in this proximal end region can create a step-up in outerdiameter.

The distal end of the proximal extension 230 and/or the distal luminalportion 222 may have features that facilitate a mechanical joint duringa weld, such as a textured surface, protruding features, or cut-outfeatures. During a heat weld process, the features would facilitate amechanical bond between the polymer distal luminal portion 222 and theproximal extension 230. For example, as shown in FIGS. 6A-6F theproximal end of the distal luminal portion 222 can include a shortmating sleeve 240 coupled to a proximal edge 221 of the distal luminalportion 222. The sleeve 240 can include an inner lumen extending betweena proximal opening 242 and a distal opening 241. The distal end of theproximal extension 230 can insert through the proximal opening 242 andwithin the inner lumen of the sleeve 240 to couple the proximalextension 230 to the distal luminal portion 222. In someimplementations, the proximal extension 230 can couple with the distalluminal portion 222 such that a distal opening 231 of the hypotubeforming the proximal extension 230 can communicate with the lumen 223 ofthe distal luminal portion 222, for example, through the distal opening241 of the sleeve 240. The sleeve 240 can also provide transitionbetween distal luminal portion 222 and proximal extension 230 similar tothe trough 238. The distal luminal portion 222 need not include a matingsleeve 240 to couple with the proximal extension 230. For example, thedistal end of the proximal extension 230 can insert through a wall ofthe trough 238 at the proximal end of the distal luminal portion 222(see FIG. 5A, 5E-5F). The distal end of the proximal extension 230 canextend along the length of the trough 238 and along at least a length ofthe wall of the distal luminal portion 222.

The luminal portion 222 of the catheter 200 can have a uniform diameteror wall thickness from a proximal end to a distal end or the luminalportion 222 can have different outer diameters or wall thicknesses alongits length. For example, the distal-most end of the distal luminalportion 222 can have a smaller outer diameter compared to a moreproximal region of the distal luminal portion 222. FIGS. 5A-5B, 5E-5F aswell as FIGS. 6A-6B, 6E-6F, and FIG. 8A show a distal luminal portion222 having a distal tubular region or distal tube 245 having a smallerouter diameter and a proximal tubular region or proximal tube 246 have alarger outer diameter. The distal tube 245 transitions via a step-up 247to the proximal tube 246. As best shown in FIGS. 5A and 6A, the innerdiameters of distal tube 245 and the proximal tube 246 are substantiallythe same providing a smooth inner wall surface for the lumen 223. Theouter diameter of the distal tube 245 may be smaller than the outerdiameter of the proximal tube 246. The step-up 247 is formed by atransition in wall thickness between the distal tube 245 and theproximal tube 246. In some implementations, the outer diameter of thedistal tube 245 can be about 0.080″ to about 0.084″ and the outerdiameter of the proximal tube 246 can be about 0.087″ to about 0.088″.In other implementations, the outer diameter of the proximal tube 246can be 0.106″ to about 0.107″. The relative lengths of the proximal anddistal tubes 245, 246 may vary as described elsewhere herein. Forexample, the proximal tube 246 can create a proximal sealing zone thatis a cylindrical segment having a length that is about 1 mm, 2 mm, 3 mm,4 mm, 5 mm, up to about 10 mm, or 15 mm. The proximal sealing zone ofthe proximal tube 246 may have a larger OD compared to the OD of thedistal tube. In some implementations, the distal tube may have an ODthat is about 0.082″, the proximal tube 246 at the proximal sealing zonemay have an OD that is about 0.087″. In other implementations, where thedistal tube may have an OD that is about 0.102″, and the proximal tube246 at the proximal sealing zone may have an OD that is about 0.105″.

At least a portion of the wall of the larger outer diameter proximaltube 246 can be discontinuous such that it includes a slit 236 (seeFIGS. 5A-5C, 5E-5F, 6A-6C, and 6E-6F). The slit 236 can extend adistance along the length of the proximal tube 246. The slit 236 canextend from an edge 221 of the proximal tube 246 at least about 2 cm ofa length of the proximal tube 246. The slit 236 can, but need not,extend along the entire length of the proximal tube 246 to the locationof the step-up 247. Additionally, the proximal tube 246 can include morethan one slit 236. The slit 236 can be positioned in the larger diameterproximal tube 246 at a location opposite from where the distal end ofthe proximal extension 230 couples with the wall of the distal luminalportion 222. As such that distal end of the proximal extension 230embedded within the wall of the proximal tube 246 lies opposite the slit236 (see FIGS. 5C and 6C). The slit 236 can be positioned around theproximal tube 246 at another location.

The slit 236 can allow for the proximal tube 246 to expand slightly suchthat the ends of the wall forming the slit 236 separate forming a gaptherebetween. For example, upon insertion of the catheter 200 throughthe working lumen of the sheath 400, the outer diameter can be receivedin a sliding fit such that at least an overlap region 348 remains. Uponapplication of an aspirational force through the working lumen, forexample, by applying suction from an aspiration source coupled to theproximal end 403 of the guide sheath 400, the sealing provided at theoverlap region 348 can be enhanced by a slight widening of the gapformed by the slit 236. This slight expansion provides for bettersealing between the outer diameter of the proximal tube 246 and theinner diameter of the working lumen of the sheath 400 because the outersurface of the walls of the catheter 200 can press against the innersurface of the working lumen creating a tight fit between the catheter200 and the sheath 400. This improved sealing between the outer surfaceof the catheter 200 and the inner surface of the working lumen minimizesthe seepage of blood from the vessel into the working lumen directlythrough the distal opening 408. Thus, the larger outer diameter of theproximal tube 246 in combination with the slit 236 can enhance sealingbetween the catheter 200 and the sheath 400 by accommodating forvariations of sheath inner diameters. The slit 236 can effectivelyincrease the outer diameter of the proximal tube 246 depending onwhether the walls forming the slit 236 are separated a distance. Thewalls forming the slit 236 can separate away from one another andincrease a width of slit. The outer diameter of the proximal tube 246including the increased width upon separation of the walls forming theslit 236 can be the same size or larger than the inner diameter of thesheath through which the proximal tube 246 is inserted. This allows fora single catheter to be compatible with a larger range of innerdiameters. In some implementations, the outer diameter of the proximaltube 246 can be 0.081″ or about 0.100″ when the walls forming the slit236 abut one another and no gap is present. The outer diameter of theproximal tube 246 can increase up to about 0.087″ or up to about 0.106″when the walls forming the slit 236 are separated a maximum distanceaway from one another. Additionally, the increased wall thickness of theproximal tube 246 allows for creating a more robust joint between thedistal luminal portion 222 and the proximal extension 230 of thecatheter.

Additionally or alternatively, the distal tip 406 of the sheath 400 caninclude one or more features that improve sealing between the innerdiameter of the working lumen of the sheath 400 and the outer diameterof the proximal end region of the catheter 200, as described elsewhereherein.

Catheter Advancement Element

As mentioned above, the distal access system 100 can, but need not,include a catheter advancement element 300 for delivery of the catheter200 to the distal anatomy. Where the catheter 200 is described herein asbeing used together or advanced with the catheter advancement element300 that the catheter advancement element 300 need not be used todeliver the catheter 200 to a target location. For example, otheradvancement tools are to be considered herein, such as a microcatheterand/or guidewire as is known in the art. Similarly, the catheteradvancement element 300 can be used together to advance other cathetersbesides the catheter 200 described herein. For example, the catheteradvancement element 300 can be used to deliver a 5MAX ReperfusionCatheter (Penumbra, Inc. Alameda, Calif.) for clot removal in patientswith acute ischemic stroke or other reperfusion catheters known in theart. Although the catheter advancement element 300 is described hereinin reference to catheter 200 it can be used to advance other cathetersand it is not intended to be limiting to its use.

As described above, the distal access system 100 is capable of providingquick and simple access to distal target anatomy, particularly thetortuous anatomy of the cerebral vasculature. The flexibility anddeliverability of the distal access catheter 200 allow the catheter 200to take the shape of the tortuous anatomy and avoids exertingstraightening forces creating new anatomy. The distal access catheter200 is capable of this even in the presence of the catheter advancementelement 300 extending through its lumen. Thus, the flexibility anddeliverability of the catheter advancement element 300 is on par orbetter than the flexibility and deliverability of the distal luminalportion 222 of the distal access catheter 200 in that both areconfigured to reach the middle cerebral artery (MCA) circulation withoutstraightening out the curves of the anatomy along the way.

The catheter advancement element 300 can include a non-expandable,flexible elongate body 360 coupled to a proximal portion 366. Thecatheter advancement element 300 and the catheter 200 described hereinmay be configured for rapid exchange or over-the-wire methods. Forexample, the flexible elongate body 360 can be a tubular portionextending the entire length of the catheter advancement element 300 andcan have a proximal opening from the lumen of the flexible elongate body360 that is configured to extend outside the patient's body during use.Alternatively, the tubular portion can have a proximal openingpositioned such that the proximal opening remains inside the patient'sbody during use. The proximal portion 366 can be a proximal elementcoupled to a distal tubular portion and extending proximally therefrom.A proximal opening from the tubular portion can be positioned near wherethe proximal element couples to the tubular portion. Alternatively, theproximal portion 366 can be a proximal extension of the tubular portionhaving a length that extends to a proximal opening near a proximalterminus of the catheter advancement element 300 (i.e. outside apatient's body).

The configuration of the proximal portion 366 can vary. In someimplementations, the proximal portion 366 is simply a proximal extensionof the flexible elongate body 360 that does not change significantly instructure but in flexibility. For example, the proximal portion 366transitions from the very flexible distal regions of the catheteradvancement element 300 towards less flexible proximal regions of thecatheter advancement element 300. The proximal portion 366 provides arelatively stiff proximal end suitable for manipulating and torqueingthe more distal regions of the catheter advancement element 300. Inother implementations, the proximal portion 366 is a hypotube. Thehypotube may be exposed or may be coated by a polymer. In still furtherimplementations, the proximal portion 366 may be a polymer portionreinforced by a coiled ribbon. The proximal portion 366 can have thesame outer diameter as the flexible elongate body or can have a smallerouter diameter as the flexible elongate body.

The proximal portion 366 need not include a lumen. For example, theproximal portion 366 can be a solid rod, ribbon, or wire have no lumenextending through it that couples to the tubular elongate body 360.Where the proximal portion 366 is described herein as having a lumen, itshould be appreciated that the proximal portion 366 can also be solidand have no lumen. The proximal portion 366 is generally less flexiblethan the elongate body 360 and can transition to be even more stifftowards the proximal-most end of the proximal portion 366. Thus, thecatheter advancement element 300 can have an extremely soft and flexibledistal-most tip that transitions proximally to a stiff proximal portion366 well suited for torqueing and pushing the distal elongate body 360.The transition in flexibility of the catheter advancement element 300and the system as a whole is described in more detail below.

The elongate body 360 can be received within and extended through theinternal lumen 223 of the distal luminal portion 222 of the catheter 200(see FIG. 2B). The elongate body 360 or tubular portion can have anouter diameter. The outer diameter of the tubular portion can have atleast one snug point, a difference between the inner diameter of thecatheter 200 and the outer diameter of the tubular portion at the snugpoint can be no more than about 0.010″, for example, from 0.003″ up toabout 0.010″, preferably about 0.006″ to about 0.008″. As will bedescribed in more detail below, the catheter advancement element 300 canalso include a tip portion or distal tip 346 located distal to the atleast one snug point of the tubular portion. The tip portion can have alength and taper along at least a portion of the length. The distal tip346 of the catheter advancement element 300 can be extended beyond thedistal end of the catheter 200 as shown in FIG. 2B. The proximal portion366 of the catheter advancement element 300 is coupled to a proximal endregion of the elongate body 360 and extends proximally therefrom. Theproximal portion 366 can be less flexible than the elongate body 360 andconfigured for bi-directional movement of the elongate body 360 of thecatheter advancement element 300 within the luminal portion 222 of thecatheter 200, as well as for movement of the catheter system 100 as awhole. The elongate body 360 can be inserted in a coaxial fashionthrough the internal lumen 223 of the luminal portion 222. The outerdiameter of at least a region of the elongate body 360 can be sized tosubstantially fill at least a portion of the internal lumen 223 of theluminal portion 222.

The overall length of the catheter advancement element 300 (e.g. betweenthe proximal end through to the distal-most tip) can vary, but generallyis long enough to extend through the support catheter 200 plus at leasta distance beyond the distal end of the support catheter 200 while atleast a length of the proximal portion 366 remains outside the proximalend of the guide sheath 400. In some implementations, the overall lengthof the catheter advancement element 300 is about 145 to about 150 cm andhas a working length of 140 cm to about 145 cm from a proximal tab orhub to the distal-most tip. The elongate body 360 can have a length thatis at least as long as the luminal portion 222 of the catheter 200although the elongate body 360 can be shorter than the luminal portion222 so long as at least a length remains inside the luminal portion 222when a distal portion of the elongate body 360 is extended distal to thedistal end of the luminal portion 222. In some implementations, thisminimum length of the elongate body 360 that remains inside the luminalportion 222 when the distal tip 346 is positioned at its optimaladvancement configuration is at least about 5 cm, at least about 6 cm,at least about 7 cm, at least about 8 cm, at least about 9 cm, at leastabout 10 cm, at least about 11 cm, or at least about 12 cm up to about50 cm. In some implementations, the shaft length of the distal luminalportion 222 can be about 35 cm up to about 75 cm and shorter than aworking length of the guide sheath and the insert length of the elongatebody 360 can be at least about 45 cm, 46 cm, 47 cm, 48 cm, 48.5 cm, 49cm, 49.5 cm, up to about 85 cm.

The length of the elongate body 360 can allow for the distal end of theelongate body 360 to reach cerebrovascular targets within, for example,the M1 or M2 regions while the proximal end region of the elongate body360 remains proximal to or below the level of severe turns along thepath of insertion. For example, the entry location of the cathetersystem can be in the femoral artery and the target embolus can be distalto the right common carotid RCC artery, such as within the M1 segment ofthe middle cerebral artery on the right side. The proximal end region ofthe elongate body 360 where it transitions to the proximal portion 366can remain within a vessel that is proximal to severely tortuous anatomysuch as the carotid siphon, the right common carotid RCC artery, thebrachiocephalic trunk BT, the take-off into the brachiocephalic arteryfrom the aortic arch, the aortic arch AA as it transitions from thedescending aorta DA. This avoids inserting the stiffer proximal portion366, or the material transition between the stiffer proximal portion 366and the elongate body 360, from taking the turn of the aortic arch orthe turn of the brachiocephalic take-off from the aortic arch, whichboth can be very severe. The lengths described herein for the distalluminal portion 222 also can apply to the elongate body 360 of thecatheter advancement element.

The proximal portion 366 can have a length that varies as well. In someimplementations, the proximal portion 366 is about 90 cm up to about 95cm. The distal portion extending distal to the distal end of the luminalportion 222 can include distal tip 346 that protrudes a length beyondthe distal end of the luminal portion 222 during use of the catheteradvancement element 300. The distal tip 346 of the elongate body 360that is configured to protrude distally from the distal end of theluminal portion 222 aids in the navigation of the catheter systemthrough the tortuous anatomy of the cerebral vessels, as will bedescribed in more detail below. The proximal portion 366 coupled to andextending proximally from the elongate body 360 can align generallyside-by-side with the proximal extension 230 of the catheter 200. Thearrangement between the elongate body 360 and the luminal portion 222can be maintained during advancement of the catheter 200 through thetortuous anatomy to reach the target location for treatment in thedistal vessels and aids in preventing the distal end of the catheter 200from catching on tortuous branching vessels, as will be described inmore detail below.

In some implementations, the elongate body 360 can have a region ofrelatively uniform outer diameter extending along at least a portion ofits length and the distal tip 346 tapers down from the uniform outerdiameter. The outer diameter of the elongate body 360 can include astep-down at a location along its length, for example, a step-down inouter diameter at a proximal end region where the elongate body 360couples to the proximal portion 366. Depending upon the inner diameterof the catheter 200, the clearance between the catheter 200 and theouter diameter of the elongate body 360 along at least a portion of itslength can be no more than about 0.010″, such as within a range of about0.003″-0.010″ or between 0.006″-0.008″.

The elongate body 360 can have an overall shape profile from proximalend to distal end that transitions from a first outer diameter having afirst length to a tapering outer diameter having a second length. Thefirst length of this first outer diameter region (i.e. the snug-fittingregion between the distal luminal portion 222 and the elongate body 360)can be at least about 5 cm, or 10 cm, up to about 50 cm. The length ofthe tapering outer diameter can be between 1 cm and 4 cm. When thecatheter advancement element 300 is inserted through the catheter 200,this tapered distal tip 346 is configured to extend beyond and protrudeout through the distal end of the luminal portion 222 whereas the moreproximal region of the body 360 having a uniform diameter remains withinthe luminal portion 222. As mentioned, the distal end of the luminalportion 222 can be blunt and have no change in the dimension of theouter diameter whereas the distal tip 346 can be tapered providing anoverall elongated tapered geometry of the catheter system. The outerdiameter of the elongate body 360 also approaches the inner diameter ofthe luminal portion 222 such that the step up from the elongate body 360to the outer diameter of the luminal portion 222 is minimized.Minimizing this step up prevents issues with the lip formed by thedistal end of the luminal portion 222 catching on the tortuousneurovasculature, such as around the carotid siphon near the ophthalmicartery branch, when the distal tip 346 bends and curves along within thevascular anatomy. In some implementations, the inner diameter of theluminal portion 222 can be at least about 0.052″, about 0.054″ and themaximum outer diameter of the elongate body 360 can be about 0.048″ suchthat the difference between them is about 0.006″. In someimplementations, the inner diameter of the luminal portion 222 can be0.070″ and the outer diameter of the elongate body 360 can be 0.062″such that the difference between them is about 0.008″. In someimplementations, the inner diameter of the luminal portion 222 can be0.088″ and the outer diameter of the elongate body 360 can be 0.080″such that the difference between them is about 0.008″. In someimplementations, the inner diameter of the luminal portion 222 can be0.072″ and the outer diameter of the elongate body 360 is 0.070″ suchthat the difference between them is about 0.002″. In otherimplementations, the outer diameter of the elongate body 360 is 0.062″such that the difference between them is about 0.010″. Despite the outerdiameter of the elongate body 360 extending through the lumen of theluminal portion 222, the luminal portion 222 and the elongate body 360extending through it in co-axial fashion are flexible enough to navigatethe tortuous anatomy leading to the level of M1 or M2 arteries withoutkinking and without damaging the vessel.

As mentioned above, each of the distal luminal portion 222 of thecatheter 200 and the elongate body 360 of the catheter advancementelement 300 are capable of bending up to about 180 degrees withoutkinking or ovalizing such that they can be folded over onto themselvesforming an inner and an outer radius of curvature. Additionally, thecombined system of the elongate body 360 extending through the lumen ofthe distal luminal portion 222 maintains this high degree of flexibilitywhen the components are assembled into a coaxial system. The twocomponents as a system can be folded and maintain similar flexibility aseach component individually. The radius of curvature of the foldedsystem is comparable to the radius of curvature of the componentsindividually. The flexibility of the two components when assembledtogether as a system allows for the system to be folded over on top ofitself such that a width across the catheter bodies is less than aminimum width without kinking or ovalizing. As an example, the distalluminal portion 222 can have an outer diameter of about 0.082″ and aninner diameter of about 0.071″. A catheter advancement element 300inserted through the distal luminal portion 222 can have an outerdiameter of about 0.062″ substantially filling the inner diameter of thedistal luminal portion 222. The catheter advancement element 300 canhave an inner diameter of about 0.019″ such that the wall thickness inthis region can be about 0.043″. When the catheter advancement element300 is assembled with the distal luminal portion 222 of the catheter andthe system folded over on itself (i.e., urged into an 180 degree bend),the maximum width across the system can be less than about 0.20″ or lessthan about 5 mm without ovalizing of either component forming theassembled system. The outer radius of curvature of the assembled systemalong the bend can be about 0.10″.

As another example, the distal luminal portion 222 can have an outerdiameter of about 0.102″ and an inner diameter of about 0.089″. Acatheter advancement element 300 inserted through the distal luminalportion 222 can have an outer diameter of about 0.080″ substantiallyfilling the inner diameter of the distal luminal portion 222. Thecatheter advancement element 300 can have an inner diameter of about0.019″ such that the wall thickness in this region can be about 0.061″.When the catheter advancement element 300 is assembled with the distalluminal portion 222 of the catheter and the system folded over on itself(i.e., urged into an 180 degree bend), the maximum width across thesystem can be less than about 0.25″ or less than about 6.4 mm withoutovalizing of either component forming the assembled system. The outerradius of curvature of the assembled system along the bend can be about0.13″.

The dimensions provided herein are approximate and each dimensions mayhave an engineering tolerance or a permissible limit of variation. Useof the term “about” or “approximately” are intended to provide suchpermissible tolerance to the dimension being referred to. Where “about”or “approximately” is not used with a particular dimension herein thatthat dimension need not be exact.

The catheter advancement element 300 can include a distal tip 346 thattapers over a length. The elongate body 360 of the catheter advancementelement 300 can have an inner diameter that does not change over itslength even in the presence of the tapering of the distal tip 346. Thus,the inner diameter of the lumen extending through the tubular portion ofthe catheter advancement element 300 can remain uniform and the wallthickness of the distal tip 346 can decrease to provide the taper. Thewall thickness can thin distally along the length of the taper. Thus,the material properties in combination with wall thickness, angle,length of the taper can all contribute to the overall maximumflexibility of the distal-most end of the distal tip 346. The catheteradvancement element 300 undergoes a transition in flexibility from thedistal-most end towards the snug point where it achieves an outerdiameter that is no more than about 0.010″ different from the innerdiameter of the catheter 200.

The length of the distal tip 346 (e.g. the region of the catheteradvancement element 300 configured to extend distal to the distal end ofthe catheter 200 during use) can vary. In some implementations, thelength of the distal tip 346 can be in a range of between about 0.50 cmand about 4.0 cm from the distal-most terminus of the elongate body 360.In other implementations, the length of the distal tip 346 is at leastabout 0.8 cm. In other implementations, the length of the distal tip 346is between 2.0 cm to about 2.5 cm. In some implementations, the lengthof the distal tip 236 varies depending on the inner diameter of theelongate body 360. For example, the length of the distal tip 236 can beas short as 0.5 cm and the inner diameter of the catheter 200 can be0.054″. The distal tip 346 can be a constant taper from the outerdiameter of the elongate body 360 down to a second smaller outerdiameter at the distal-most tip. In some implementations, the constanttaper of the distal tip 346 can be from about 0.048″ outer diameter downto about 0.031″ outer diameter that tapers to about 65% of the largestdiameter. In some implementations, the constant taper of the distal tip346 can be from 0.062″ outer diameter to about 0.031″ outer diameterthat tapers to about half of the largest diameter. In still furtherimplementations, the constant taper of the distal tip 346 can be from0.080″ outer diameter to about 0.031″ outer diameter that tapers toabout 40% of the largest diameter. The length of the constant taper ofthe distal tip 346 can vary, for example, about 0.5 cm to about 4.0 cm,or about 0.8 cm to about 3.5 cm, or about 1 cm to about 3 cm, or about2.0 cm to about 2.5 cm. The angle of the taper can vary depending on theouter diameter of the elongate body 360. For example, the taper angle ofthe wall of the tapered portion of the flexible elongate body can bebetween 0.9 to 1.6 degree angle relative to horizontal. The taper angleof the wall of the tapered portion of the flexible elongate body can bebetween 2-10 degrees or 2-3 degree angle from a center line of theelongate body 360.

The distal tip 346 need not taper and can achieve its soft, atraumaticand flexible characteristic due to a material property other than due toa change in outer dimension to facilitate endovascular navigation to anembolus in tortuous anatomy. Additionally or alternatively, the distaltip 346 of the elongate body 360 can have a transition in flexibilityalong its length. The most flexible region of the distal tip 346 can beits distal terminus. Moving along the length of the distal tip 346 fromthe distal terminus towards a region proximal to the distal terminus,the flexibility can gradually approach the flexibility of the distal endof the luminal portion 222. For example, the distal tip 346 can beformed of a material having a hardness of no more than 35 D or about 62A and transitions proximally towards increasingly harder materialshaving a hardness of no more than 55 D and 72 D up to the proximalportion 366, which can be a stainless steel hypotube, or a combinationof a material property and tapered shape. The hypotube can be coatedwith one or more polymers. The hypotube of the proximal portion 366 canbe fully enclosed stainless steel tube having an inner lumen or can betubular with one or more interruptions or perforations or cuts through asidewall (e.g., by laser cutting, micromachining and the like). Thehypotube of the proximal portion 366 can define a lumen along at least aportion of its length and/or can be at least partially solid having nolumen along at least a portion of its length. In still furtherimplementations, the proximal portion 366 can be at least partly solidand at least partly a hypotube, optionally wherein the hypotubeincorporates one or more interruptions or cuts. The proximal portion 366need not include a hypotube. The proximal portion 366 hypotube caninclude a material such as Nitinol in lieu of or in addition tostainless steel. In still further implementations, the catheteradvancement element 300 need not include any metallic structure withinits proximal portion 366 or within its elongate body 360. The catheteradvancement element 300 can be formed completely of polymeric materialswhere the elongate body 360 is unreinforced polymeric material and theproximal portion 366 is a reinforced polymeric material. Thereinforcement of the reinforced polymer can also be polymeric providingadditional rigidity to the proximal portion 366 compared to theunreinforced polymer of the elongate body 360. The reinforced polymer ofthe proximal portion 366 can also include reinforcement structures suchas a braid, coil, or other reinforcement structure or combination ofstructures. The reinforcement structures can be metallic or nonmetallicreinforcement.

The materials used to form the regions of the elongate body 360 caninclude PEBAX elastomers in the Shore D to Shore A hardness ranges (suchas PEBAX 25 D, 35 D, 40 D, 45 D, 55 D, 63 D, 70 D, 72 D) with or withouta lubricious additive compound, such as Mobilize (Compounding Solutions,Lewiston, Me.). In some implementations, the material used to form aregion of the elongate body 360 can be an aromatic polyether-basedthermoplastic polyurethane (e.g., Tecothane, Lurbizol) in a Shore Ahardness range of 90 A, 85 A, 75 A, 62 A, 50 A. Incorporation of alubricious additive directly into the polymer elongate body meansincorporation of a separate lubricious liner, such as a Teflon liner, isunnecessary. Thus, the flexible elongate body 360 can be formed withouta tubular inner liner. The flexible elongate body 360 can be formedwithout an inner liner at the inner diameter that is sized toaccommodate a guidewire. This allows for a more flexible element thatcan navigate the distal cerebral anatomy and is less likely to kink.Similar materials can be used for forming the distal luminal portion 222of the catheter 200 providing similar advantages. It should also beappreciated that the flexibility of the distal tip 346 can be achievedby a combination of flexible lubricious materials and tapered shapes.For example, the length of the tip 346 can be kept shorter than 2 cm-3cm, but maintain optimum deliverability due to a change in flexiblematerial from distal-most tip towards a more proximal region a distanceaway from the distal-most tip. In an implementation, the elongate body360 is formed of PEBAX (polyether block amide) embedded siliconedesigned to maintain the highest degree of flexibility. The wallthickness of the distal end of the luminal portion 222 can also be madethin enough such that the lip formed by the distal end of the luminalportion 222 relative to the elongate body 360 is minimized.

The flexible elongate body 360 of the catheter advancement element 300(sometimes referred to herein as a device 300) can include a proximalend, a distal end, and a single lumen extending therebetween. Theflexible elongate body 360 can include a proximal segment or proximalportion 366 that include a hypotube coated with a polymer. The flexibleelongate body 360 can also include an intermediate segment that is anunreinforced polymer having a durometer of no more than 72 D, forexample, 55 D or a blend of 55 D and 35 D. The flexible elongate body360 can include a tip segment that is also formed of a polymer, but thatis different from the polymer of the intermediate segment and that has adurometer of no more than about 35 D. The tip segment can have a lengthof at least 5 cm, for example, 5 cm up to about 20 cm. The tip segmentcan include a tapered portion 346 that tapers distally from a firstouter diameter to a second outer diameter over a length of about 0.5 cmto about 4 cm, or about 1 cm to about 3 cm, or about 2 cm to about 2.5cm. The catheter advancement element 300 can have a length configured toextend from outside the patient's body at the access site, through thefemoral artery and to a petrous portion of the internal carotid arteryas described elsewhere herein. The inner diameter of the catheteradvancement element 300 can accommodate a guidewire. The ID can be lessthan 0.024″ or between about 0.019″ to about 0.021″. The intermediatesegment can include a first segment having a material hardness of nomore than about 55 D and a second segment located proximal to the firstsegment having a material hardness of no more than 72 D. The proximalregion hypotube can form a single continuous lumen from the intermediatesegment to a proximal-most end, such as a proximal hub. The hypotube canbe an uncut hypotube or can be cut as described elsewhere herein. Thehypotube can be a stainless steel hypotube. The flexible elongate bodycan be formed without a tubular inner liner and the unreinforced polymerof the flexible elongate body can incorporate a lubricious additive.

As mentioned above, the elongate body 360 can be constructed to havevariable stiffness between the distal and proximal ends of the elongatebody 360. The flexibility of the elongate body 360 is highest at thedistal-most terminus of the distal tip 346 and can gradually transitionin flexibility to approach the flexibility of the distal end of theluminal portion 222, which is typically less flexible than thedistal-most terminus of the distal tip 346. Upon inserting the catheteradvancement element 300 through the catheter 200, the region of theelongate body 360 extending beyond the distal end of the luminal portion222 can be the most flexible and the region of the elongate body 360configured to be aligned with the distal end of the luminal portion 222during advancement in the vessel can have a substantially identicalflexibility as the distal end of the luminal portion 222 itself. Assuch, the flexibility of the distal end of the luminal portion 222 andthe flexibility of the body 360 just proximal to the extended portion(whether tapered or having no taper) can be substantially the same. Thisprovides a smooth transition in material properties to improve trackingof the catheter system through tortuous anatomy. Further, the moreproximal sections of the elongate body 360 can be even less flexible andincreasingly stiffer. The change in flexibility of the elongate body 360can be a function of a material difference, a dimensional change such asthrough tapering, or a combination of the two. The elongate body 360 hasa benefit over a microcatheter in that it can have a relatively largeouter diameter that is just 0.003″-0.010″ smaller than the innerdiameter of the distal luminal portion 222 of the catheter 200 and stillmaintain a high degree of flexibility for navigating tortuous anatomy.When the gap between the two components is too tight (e.g. less thanabout 0.003″), the force needed to slide the catheter advancementelement 300 relative to the catheter 200 can result in damage to one orboth of the components and increases risk to the patient during theprocedure. The gap results in too tight of a fit to provide optimumrelative sliding. When the gap between the two components is too loose(e.g. greater than about 0.010″), the distal end of the catheter 200forms a lip that is prone to catch on branching vessels duringadvancement through tortuous neurovasculature, such as around thecarotid siphon where the ophthalmic artery branches off.

The gap in ID/OD between the elongate body 360 and the distal luminalportion 222 can be in this size range (e.g. 0.003″-0.010″) along amajority of their lengths. For example, the elongate body 360 can have arelatively uniform outer diameter that is between about 0.048″ to about0.080″ from a proximal end region to a distal end region up to a pointwhere the taper of the distal tip 346 begins. Similarly, the distalluminal portion 222 of the catheter 200 can have a relatively uniforminner diameter that is between about 0.054″ to about 0.088″ from aproximal end region to a distal end region. As such, the differencebetween their respective inner and outer diameters along a majority oftheir lengths can be within this gap size range of 0.003″ to 0.010″. Thedistal tip 346 of the elongate body 360 that is tapered will have alarger gap size relative to the inner diameter of the distal luminalportion 222. During use, however, this tapered distal tip 346 isconfigured to extend distal to the distal end of the catheter 200 suchthat the region of the elongate body 360 having an outer diameter sizedto match the inner diameter of the distal luminal portion 222 ispositioned within the lumen of the catheter 200 such that it canminimize the lip at the distal end of the catheter 200.

The elongate body 360 can be formed of various materials that provide asuitable flexibility and lubricity. Example materials include highdensity polyethylene, 72 D PEBAX, 90 D PEBAX, or equivalent stiffnessand lubricity material. At least a portion of the elongate body 360 canbe reinforced to improve navigation and torqueing (e.g. braidedreinforcement layer). The flexibility of the elongate body 360 canincrease towards the distal tip 346 such that the distal region of theelongate body 360 is softer, more flexible, and articulates and bendsmore easily than a more proximal region. For example, a more proximalregion of the elongate body can have a bending stiffness that isflexible enough to navigate tortuous anatomy such as the carotid siphonwithout kinking. In some implementations, the elongate body 360 is afully polymeric structure (except perhaps the presence of one or moreradiomarkers) without any reinforcement, particularly in distal regionsof the elongate body 360. The fully polymeric, unreinforced distalregion of the elongate body 360 provides a particularly low bendingstiffness range described elsewhere herein that results in the catheteradvancement element 300 being particularly suitable for navigationthrough tortuous anatomy (e.g., 180 degrees around a radius as small as2 mm without kinking). In other implementations, the elongate body 360incorporates a reinforcement layer that can extend up to the distal tip346 or can extend a distance short of the distal tip 346. If theelongate body 360 has a braid reinforcement layer along at least aportion of its length, the braid reinforcement layer can terminate adistance proximal to the distal tip 346. For example, the distance fromthe end of the braid to the distal tip can be about 10 cm to about 15 cmor from about 4 cm to about 10 cm or from about 4 cm up to about 15 cm.The reinforcement layer can be metallic or nonmetallic material. Instill other implementations, the reinforcement can extend all the way tothe distal tip 346. The shore hardness of the polymer segments withinthe distal tip 346 can be reduced to offset or compensate for theadditional stiffness due to the presence of the reinforcement. Thisallows for the reinforced distal tip 346 to maintain a flexibility andlow bending force range that is still suitable for navigation throughtortuous anatomy. The reinforcement (e.g., braid, coil, or combination)can extending along the length of the catheter advancement element 300(up to or excluding the distal tip 346). The catheter advancementelement 300 can also include one or more distinct regions ofreinforcement along one or more points of its length. For example, oneor more distinct coils or bands of reinforcement can be incorporatedthat encircle the catheter advancement element 300. The band can coveronly a short length of the element 300 that is as wide as the banditself as opposed to windings of a ribbon forming a plurality of coilsover a greater length. The distinct bands can be located within one ormore regions of the proximal portion 366 and/or within one or moreregions of the elongate body 360.

Where the catheter advancement element is described herein as beingfully polymeric and having no metallic structure for reinforcement orotherwise, the catheter advancement element may still incorporate one ormore radiopaque markers to identify particular locations along itslength. A fully polymeric catheter advancement element 300 or a fullypolymeric elongate body 360 of the catheter advancement element 300 mayadditionally include radiopaque contrast material embedded in or coatingthe polymer including barium sulfate, bismuth compounds, tungsten,platinum/iridium, tantalum, platinum, and other metallic materials thatabsorb x-rays.

In some implementations, the elongate body 360 can be generally tubularalong at least a portion of its length such that it has a single lumen368 extending parallel to a longitudinal axis of the catheteradvancement element 300 (see FIG. 7A-7C and also FIG. 10A-10C). In animplementation, the single lumen 368 of the elongate body 360 is sizedto accommodate a guidewire, however use of the catheter advancementelement 300 generally eliminates the need for a guidewire lead. Theguidewire can extend through the single lumen 368 generallyconcentrically from a proximal opening to a distal opening through whichthe guidewire can extend. In some implementations, the proximal openingis at the proximal end of the catheter advancement element 300 such thatthe catheter advancement element 300 is configured for over-the-wire(OTW) methodologies. In other implementations, the proximal opening is arapid exchange opening 362 through a wall of the catheter advancementelement 300 such that the catheter advancement element 300 is configuredfor rapid exchange rather than or in addition to OTW. In thisimplementation, the proximal opening 362 extends through the sidewall ofthe elongate body and is located a distance away from a proximal tab 364and distal to the proximal portion 366 (see FIGS. 7A-7B and 7D). Theproximal opening 362 can be located a distance of about 10 cm from thedistal tip 346 up to about 20 cm from the distal tip 346. In someimplementations, the proximal opening 362 can be located near a regionwhere the elongate body 360 is joined to the proximal portion 366, forexample, just distal to an end of the hypotube (see FIG. 7B). In otherimplementations, the proximal opening 362 is located more distally suchas about 10 cm to about 18 cm from the distal-most end of the elongatebody 360 (see FIG. 7D). A proximal opening 362 that is located closer tothe distal tip 346 allows for easier removal of the catheter advancementelement 300 from the catheter 200 leaving the guidewire in place for a“rapid exchange” type of procedure. Rapid exchanges can rely on only asingle person to perform the exchange. The catheter advancement element300 can be readily substituted for another device using the sameguidewire that remains in position. The single lumen 368 of the elongatebody 360 can be configured to receive a guidewire having an outerdiameter from about 0.010″ up to about 0.024″, or in the range of 0.012″and 0.022″ outer diameter, or in the range of between 0.014″ and 0.020″outer diameter. The single lumen 368 of the elongate body 360 can havean inner diameter at the distal tip (i.e., the size of the distalopening from the single lumen 368) that is at least about 0.010″ up toabout 0.030″, about 0.012″ up to about 0.026″ inner diameter, or about0.016″ up to about 0.024″ inner diameter, or about 0.020″ up to about0.022″ inner diameter, or about 0.019″ and about 0.021″. The elongatebody 360 can be about 0.002″ greater, or about 0.003″ greater, or about0.004″ greater in inner diameter than the outer diameter of theguidewire. In an implementation, the guidewire outer diameter is between0.014″ and about 0.022″ and the inner luminal diameter of the elongatebody 360 is between 0.020″ and 0.024″. The difference in size betweenthe distal opening inner diameter of the elongate body 360 and the outerdiameter of the guidewire can be between about 0.002″ up to about0.010″.

The inner diameter of the elongate body 360 can be constant along itslength even where the single lumen passes through the tapering distaltip 346. Alternatively, the inner diameter of the elongate body 360 canhave a first size through the tapering distal tip 346 and a second,larger size through the cylindrical section of the elongate body 360.The cylindrical section of the elongate body 360 can have a constantwall thickness or a wall thickness that varies to a change in innerdiameter of the cylindrical section. As an example, the outer diameterof the cylindrical section of the elongate body 360 can be about 0.080″.The inner diameter of the elongate body 360 within the cylindricalsection can be uniform along the length of the cylindrical section andcan be about 0.019″. The wall thickness in this section, in turn, can beabout 0.061″. As another example, the outer diameter of the cylindricalsection of the elongate body 360 can again be between about 0.080″. Theinner diameter of the elongate body 360 within the cylindrical sectioncan be non-uniform along the length of the cylindrical section and canstep-up from a first inner diameter of about 0.019″ to a larger secondinner diameter of about 0.021″. The wall thickness, in turn, can beabout 0.061″ at the first inner diameter region and about 0.059″ at thesecond inner diameter region. The wall thickness of the cylindricalportion of the elongate body 360 can be between about 0.050″ to about0.065″. The wall thickness of the tapered distal tip 346 near thelocation of the proximal marker band can be the same as the cylindricalportion (between about 0.050″ and about 0.065″) and become thinnertowards the location of the distal marker band. As an example, the innerdiameter at the distal opening from the single lumen can be about 0.020″and the outer diameter at the distal opening (i.e. the outer diameter ofthe distal marker band) and be about 0.030″ resulting in a wallthickness of about 0.010″ compared to the wall thickness of thecylindrical portion that can be up to about 0.065″. Thus, the outerdiameter of the distal tip 346 can taper as can the wall thickness.

A tip segment of the flexible elongate body can have a tapered portionthat tapers distally from a first outer diameter to a second outerdiameter. The second outer diameter can be about ½ of the first outerdiameter. The second outer diameter can be about 40% of the first outerdiameter. The second outer diameter can be about 65% of the first outerdiameter. The first outer diameter can be about 0.062″ up to about0.080″. The second outer diameter can be about 0.031″.

The guidewire, the catheter advancement element 300, and the catheter200 can all be assembled co-axially for insertion through the workinglumen of the guide sheath 400.

FIG. 7D shows another implementation of the catheter advancement element300 configured for rapid exchange. Rapid exchange configurations candramatically shorten device length, decreases staffing requirements, andreduces fluoroscopy. As with other implementations described herein, thecatheter advancement element 300 can include a non-expandable, flexibleelongate body 360 coupled to a proximal portion 366 coupled to aproximal tab 364 or hub 375. As described elsewhere herein, the regionnear the distal tip 346 can be tapered such that the outer diametertapers over a length of about 1 cm to about 3 cm. In someimplementations, the distal taper length is 2.5 cm. In someimplementations, the distal tip 346 tapers from about 0.080″ to about0.031″. Also as described elsewhere herein, the distal tip 346 can beformed of a material having a hardness (e.g. 62 A and 35 D) thattransitions proximally towards increasingly harder materials having(e.g. 55 D and 72 D) up to the proximal portion 366. For example, FIG.7D illustrates segment 371 of the elongate body 360 including the distaltip 346 can have a hardness of 35 D and a length of about 10 cm to about12.5 cm. Segment 371 of the elongate body 360 including the distal tip346 can have a hardness of 62 A and a length of about 10 cm to about12.5 cm. Segment 372 of the elongate body 360 can have a hardness of 55D and have a length of about 5 cm to about 8 cm. Segment 373 of theelongate body 360 can have a hardness of 72 D can be about 25 cm toabout 35 cm in length. Together segments 371 and 372 can form a tipsegment that includes the tapered tip and segment 373 can form anintermediate segment. The three segments 371, 372, 373 combined can forman insert length of the elongate body 360 from where the proximalportion 366 couples to the elongate body 360 to the terminus of thedistal tip 346 that can be about 49 cm in length. A location of amaterial transition between the unreinforced polymer of an intermediatesegment of the flexible elongate body 360 and the hypotube of theproximal segment can be at least about 49 cm from the distal end of theflexible elongate body, ab least about 59 cm, at least about 69 cm, upto about 80 cm. The location of the material transition allows forpositioning the material transition proximal to the brachiocephalictake-off in the aortic arch when the distal end of the flexible elongatebody is positioned within the petrous portion of the internal carotidartery.

FIGS. 10A-10C illustrate an implementation of a catheter advancementelement 300 incorporating a reinforcement layer 380. As mentioned above,the reinforcement layer 380 can be a braid or other type ofreinforcement to improve the torqueability of the catheter advancementelement 300 and help to bridge the components of the catheteradvancement element 300 having such differences in flexibility. Thereinforcement layer 380 can bridge the transition from the rigid,proximal portion 366 to the flexible elongate body 360. In someimplementations, the reinforcement layer 380 can be a braid positionedbetween inner and outer layers of Pebax 382, 384 (see FIG. 10C). Thereinforcement layer 380 can terminate a distance proximal to the distaltip region 346. For example, FIG. 10A illustrates the elongate body 360having segment 371 and segment 373 located proximal to segment 371.Segment 371 can include the distal tip 346 having a hardness of at mostabout 35 D. Segment 371 is unreinforced polymer having a length of about4 cm up to about 12.5 cm. Segment 373 of the elongate body 360 locatedproximal to segment 371 can include the reinforcement layer 380 and canextend a total of about 37 cm up to the unreinforced distal segment 371.A proximal end region of the reinforcement layer 380 can overlap with adistal end region of the proximal portion 366 such that a small overlapof hypotube and reinforcement exists near the transition between theproximal portion 366 and the elongate body 360.

Again with respect to FIG. 7D, an entry port 362 for a proceduralguidewire 805 can be positioned a distance away from the distal-most endof the elongate body 360. In some implementations, the entry/exit port362 can be about 18 cm from the distal-most end creating a rapidexchange wire entry/exit segment 370. The outer diameter of the elongatebody 360 within segment 370 (segments 371 and 372) can be about0.080″-0.082″ whereas segment 373 proximal to this rapid exchange wireentry/exit segment 370 can have a step-down in outer diameter such asabout 0.062″-0.064″.

In other implementations, the entire catheter advancement element 300can be a tubular element configured to receive a guidewire through boththe proximal portion 366 as well as the elongate body 360. For example,the proximal portion 366 can be a hypotube or tubular element having alumen that communicates with the lumen 368 extending through theelongate body 360 (shown in FIG. 3). In some implementations, theproximal portion 366 can be a skived hypotube of stainless steel coatedwith PTFE having an outer diameter of 0.026″. In other implementations,the outer diameter can be between 0.024″ and 0.030″. In someimplementations, such as an over-the-wire version, the proximal portion366 can be a skived hypotube coupled to a proximal hub 375. The proximalportion 366 can extend eccentric or concentric to the distal luminalportion 222. As best shown in FIG. 7E, the proximal portion 366 can be astainless steel hypotube as described elsewhere herein that is baremetal or at least partially coated with a polymer or polymers. Thehypotube can be a fully enclosed stainless steel tube defining an innerlumen or can be a tubular element with one or more interruptions,perforations, and or cuts through its side wall as discussed above. Theproximal portion 366 can have a lumen along at least a portion of itslength and can be at least partly solid along its length. The proximalportion 366 need not be or include a hypotube. The proximal portion 366can be a solid metal wire that is round or oval cross-sectional shape.The proximal portion 366 can be a flattened ribbon of wire having arectangular cross-sectional shape as described elsewhere herein. Theribbon of wire can be curved into a circular, oval, c-shape, or quartercircle, or other cross-sectional shape along an arc. The proximalportion 366 can have any of variety of cross-sectional shapes whether ornot a lumen extends therethrough, including a circular, oval, C-shaped,D-shape, or other shape. In some implementations, the proximal portion366 is a hypotube having a D-shape such that an inner-facing side isflat and an outer-facing side is rounded. The rounded side of theproximal portion 366 can be shaped to engage with a correspondinglyrounded inner surface of the sheath 400. The hypotube can have alubricious coating such as PTFE. The hypotube can have an inner diameterof about 0.021″, an outer diameter of about 0.0275″, and an overalllength of about 94 cm providing a working length for the catheteradvancement element 300 that is about 143 cm. Including the proximal hub375, the catheter advancement element 300 can have an overall length ofabout 149 cm. In some implementations, the hypotube can be a taperedpart with a length of about 100 mm, starting proximal with a thicknessof 0.3 mm and ending with a thickness of 0.10 mm to 0.15 mm. In stillfurther implementations, the elongate body 360 can be a solid elementcoupled to the proximal portion 366 having no guidewire lumen.

As best shown in FIGS. 7F-7J, the proximal end of the hypotube can becoupled to a proximal hub 375. The proximal hub 375 can be anover-molded component having a luer thread 377 and a luer taper 378formed on an inside of the proximal hub 375. The proximal hub 375 canincorporate a tab 364 providing for easier gripping by a user. Theproximal hub 375 prevents advancement of the catheter advancementelement 300 and the catheter 200 beyond the distal tip of the basesheath 400 or guide catheter by limiting insertion into the proximal RHV434 providing critical functional and safety features for properoperation of the system 10.

At least a portion of the solid elongate body 360, such as the elongatedistal tip 346, can be formed of or embedded with or attached to amalleable material that skives down to a smaller dimension at a distalend. The distal tip 346 can be shaped to a desired angle or shapesimilar to how a guidewire may be used. The malleable length of theelongate body 360 can be at least about 1 cm, 3 cm, 5 cm, and up toabout 10 cm, 15 cm, or longer. In some implementations, the malleablelength can be about 1%, 2%, 5%, 10%, 20%, 25%, 50% or more of the totallength of the elongate body 360. In some implementations, the catheteradvancement element 300 can have a working length of about 140 cm toabout 143 cm and the elongate body 360 can have an insert length ofabout 49 cm. The insert length can be the PEBAX portion of the elongatebody 360 that is about 49.5 cm. As such, the malleable length of theelongate body 360 can be between about 0.5 cm to about 25 cm or more.The shape change can be a function of a user manually shaping themalleable length prior to insertion or the tip can be pre-shaped at thetime of manufacturing into a particular angle or curve. Alternatively,the shape change can be a reversible and actuatable shape change suchthat the tip forms the shape upon activation by a user such that the tipcan be used in a straight format until a shape change is desired by theuser. The catheter advancement element 300 can also include a formingmandrel extending through the lumen of the elongate body 360 such that aphysician at the time of use can mold the distal tip 346 into a desiredshape. As such, the moldable distal tip 346 can be incorporated onto anelongate body 360 that has a guidewire lumen.

The elongate body 360 can extend along the entire length of the catheter200, including the distal luminal portion 222 and the proximal extension230 or the elongate body 360 can incorporate the proximal portion 366that aligns generally side-by-side with the proximal extension 230 ofthe catheter 200, as described above. The proximal portion 366 of theelongate body 360 can be positioned co-axial with or eccentric to theelongate body 360. The proximal portion 366 of the elongate body 360 canhave a lumen extending through it. Alternatively, the portion 366 can bea solid rod or ribbon having no lumen.

Again with respect to FIGS. 7A-7D, like the distal luminal portion 222of the catheter 200, the elongate body 360 can have one or moreradiopaque markers 344 along its length. The one or more markers 344 canvary in size, shape, and location. One or more markers 344 can beincorporated along one or more parts of the catheter advancement element300, such as a tip-to-tip marker, a tip-to-taper marker, an RHVproximity marker, a Fluoro-saver marker, or other markers providingvarious information regarding the relative position of the catheteradvancement element 300 and its components. In some implementations andas best shown in FIG. 7C, a distal end region can have a firstradiopaque marker 344 a and a second radiopaque marker 344 b can belocated to indicate the border between the tapering of the distal tip346 and the more proximal region of the elongate body 360 having auniform or maximum outer diameter. This provides a user with informationregarding an optimal extension of the distal tip 346 relative to thedistal end of the luminal portion 222 to minimize the lip at this distalend of the luminal portion 222 for advancement through tortuous anatomy.In other implementations, for example where the distal tip 346 is notnecessarily tapered, but instead has a change in overall flexibilityalong its length, the second radiopaque marker 344 b can be located toindicate the region where the relative flexibilities of the elongatebody 360 (or the distal tip 346 of the elongate body 360) and the distalend of the luminal portion 222 are substantially the same. The markermaterial may be a barium sulfate, bismuth, platinum/iridium band, atungsten, platinum, or tantalum-impregnated polymer, or other radiopaquemarker that does not impact the flexibility of the distal tip 346 andelongate body 360. In some implementations, the radiopaque markers areextruded PEBAX loaded with tungsten for radiopacity. In someimplementations, the proximal marker band can be about 2.0 mm wide andthe distal marker band can be about 2.5 mm wide to provide discernableinformation about the distal tip 346. Some marker materials may impactthe flexibility of the polymer within which they are embedded. Forexample, barium sulfate tends to stiffen polymer. Thus, the polymerwhere the marker material is incorporated may have a reduced hardness toachieve a final material property for the region that remains suitablefor navigation. The distal tip 346 may incorporate a proximal endradiopaque marker that is a band of barium sulfate-loaded PEBAX that hasa final durometer of no greater than 35 D, or 25 D, or another softdurometer. The PEBAX prior to the embedding of the radiopaque materialmay have an initial durometer that is less than the final durometer. Thereduction in polymer hardness can offset the stiffening effects of themarker material so that the device maintains flexibility suitable fornavigating tortuous anatomy (e.g., tip flexibility measurement that isless than about 0.05 Newtons and/or a catheter system capable of bending180 degrees while maintaining a maximum folded width across that is lessthan about 5.0 mm without kinking or ovalizing).

As mentioned above, the proximal extension 230 of the catheter 200 caninclude a proximal tab 234 on the proximal end of the proximal extension230. Similarly, the proximal portion 366 coupled to the elongate body360 can include a tab 364. The tabs 234, 364 can be configured toremovably and adjustable connect to one another and/or connect to theircorresponding proximal portions. The coupling allows the catheteradvancement element 300 to reversibly couple with the catheter 200 tolock (and unlock) the relative extension of the distal luminal portion222 and the elongate body 360. This allows the catheter 200 and thecatheter advancement element 300 to be advanced as a single unit. In thelocked configuration, the tab 364 or proximal portion 366 can be engagedwith the catheter tab 234. In the unlocked configuration, the tab 364may be disengaged from the catheter tab 234. The tab 364 or proximalportion 366 may attach, e.g., click or lock into, the catheter tab 234in a fashion as to maintain the relationships of corresponding sectionof the elongate body 360 and the catheter 200 in the lockedconfiguration. The tab 364 can be a feature on the proximal hub 375 suchas the hub 375 shown in FIGS. 7F-7J.

Such locking may be achieved by, e.g., using a detent on the tab 364that snaps into place within a recess formed in the catheter tab 234, orvice versa. For example, the tab 234 of the catheter 200 can form a ringhaving a central opening extending therethrough. The tab 364 of the body360 can have an annular detent with a central post sized to insertthrough the central opening of the tab 234 such that such that the ringof the tab 234 is received within the annular detent of tab 364 forminga singular grasping element for a user to advance and/or withdraw thecatheter system through the access sheath. The tabs 234, 364 may beaffixed or may be slideable to accommodate different relative positionsbetween the elongate body 360 and the luminal portion 222 of thecatheter 200. In some implementations, a proximal end of the proximalextension 230 of the catheter 200 can include a coupling feature 334,such as clip, clamp, c-shaped element or other connector configured toreceive the proximal portion 366 of the catheter advancement element 300(see FIG. 2A). The coupling feature 334 can be configured to snaptogether with the proximal portion 366 through an interference fit suchthat a first level of force is needed in order to insert the proximalportion 366 into the clip of the tab 234 and a second, greater level offorce is needed to remove the proximal portion 366 from the clip of thetab 234. However, upon inserting the proximal portion 366 into thecoupling feature 334 the catheter advancement element 300 and thecatheter 200 can still be slideably adjusted relative to one anotheralong a longitudinal axis of the system. The amount of force needed toslideably adjust the relative position of the two components can be suchthat inadvertent adjustment is avoided and the relative position can bemaintained during use, but can be adjusted upon conscious modification.The configuration of the coupling between the proximal portion 366 ofthe catheter advancement element 300 and the proximal extension 360 ofthe catheter 200 can vary. Generally, however, the coupling isconfigured to be reversible and adjustable while still providingadequate holding power between the two elements in a manner that isrelatively user-friendly (e.g. allows for one-handed use) and organizesthe proximal ends of the components (e.g. prevents the proximalextension 360 and proximal portion 366 from becoming twisted andentangled with one another). It should also be appreciated that thecoupling feature 334 configured to prevent entanglement and aid in theorganization of the proximal portions can be integrated with the tabs orcan be a separate feature located along their proximal end region.

The catheter advancement element 300 can be placed in a lockedconfiguration with the catheter 200 configured for improved trackingthrough a tortuous and often diseased vasculature in acute ischemicstroke. Other configurations are considered herein. For example, theelongate body 360 can include one or more detents on an outer surface.The detents can be located near a proximal end region and/or a distalend region of the elongate body 360. The detents are configured to lockwith correspondingly-shaped surface features on the inner surface of theluminal portion 222 through which the elongate body 360 extends. Thecatheter advancement element 300 and the catheter 200 can haveincorporate more than a single point of locking connection between them.For example, a coupling feature 334, such as clip, clamp, c-shapedelement or other connector configured to hold together the catheteradvancement element 300 and proximal extension 230 or tab 234 of thecatheter 200 as described elsewhere herein.

In some implementations, the proximal extension 230 of the catheter 200can run alongside or within a specialized channel of the proximalportion 366. The channel can be located along a length of the proximalportion 366 and have a cross-sectional shape that matches across-sectional shape of the catheter proximal extension 230 such thatthe proximal extension 230 of the catheter 200 can be received withinthe channel and slide smoothly along the channel bi-directionally. Oncethe catheter 200 and elongate body 360 are fixed, the combined system,i.e., the catheter 200-catheter advancement element 300 may be deliveredto a target site, for example through the working lumen of the guidesheath 400 described elsewhere herein.

The catheter advancement element 300 (whether incorporating thereinforcement layer or not) loaded within the lumen of the catheter 200may be used to advance a catheter 200 to distal regions of the brain(e.g. level of the MCA). The traditional approach to the Circle ofWillis is to use a triaxial system including a guidewire placed within aconventional microcatheter placed within an intermediate catheter. Theentire coaxial system can extend through a base catheter or sheath. Thesheath is typically positioned such that the distal tip of the sheath isplaced in a high cervical carotid artery. The coaxial systems are oftenadvanced in unison up to about the terminal carotid artery where theconventional coaxial systems must then be advanced in a step-wisefashion in separate throws. This is due to the two sequential 180 degreeor greater turns (see FIGS. 1A-1C). The first turn is at the level ofthe petrous to the cavernous internal carotid artery. The second turn isat the terminal cavernous carotid artery as it passes through the bonyelements and reaches the bifurcation into the anterior cerebral arteryACA and middle cerebral artery MCA. This S-shape region is referred toherein as the “siphon” or “carotid siphon”. The ophthalmic artery arisesfrom the cerebral ICA, which represents a common point of catheter hangup in accessing the anterior circulation.

Conventional microcatheter systems can be advanced through to theanterior circulation over a guidewire. Because the inner diameter of theconventional microcatheter is significantly larger than the outerdiameter of the guidewire over which it is advanced, a lip can be formedon a distal end region of the system that can catch on these sidebranches during passage through the siphon. Thus, conventionalmicrocatheter systems (i.e. guidewire, microcatheter, and intermediatecatheter) are never advanced through both bends of the carotid siphonsimultaneously in a single smooth pass to distal target sites. Rather,the bends of the carotid siphon are taken one at a time in a step-wiseadvancement technique. For example, to pass through the carotid siphon,the conventional microcatheter is held fixed while the guidewire isadvanced alone a first distance (i.e. through the first turn of thesiphon). Then, the guidewire is held fixed while the conventionalmicrocatheter is advanced alone through the first turn over theguidewire. Then, the conventional microcatheter and guidewire are heldfixed while the intermediate catheter is advanced alone through thefirst turn over the microcatheter and guidewire. The process repeats inorder to pass through the second turn of the siphon, which generally isconsidered the more challenging turn into the cerebral vessel. Themicrocatheter and intermediate catheter are held fixed while theguidewire is advanced alone a second distance (i.e. through the secondturn of the siphon). Then, the guidewire and interventional catheter areheld fixed while the microcatheter is advanced alone through that secondturn over the guidewire. Then, the guidewire and the microcatheter areheld fixed while the interventional catheter is advanced alone throughthe second turn. This multi-stage, step-wise procedure is atime-consuming process that requires multiple people performing multiplehand changes on the components. For example, two hands to fix and pushthe components over each other forcing the user to stage the steps asdescribed above. The step-wise procedure is required because the steppedtransitions between these components (e.g. the guidewire, microcatheter,and intermediate catheter) makes advancement too challenging.

In contrast, the catheter 200 and catheter advancement element 300eliminate this multi-stage, step-wise component advancement procedure toaccess distal sites across the siphon. The catheter 200 and catheteradvancement element 300 can be advanced as a single unit through theboth turns of the carotid siphon CS. Both turns can be traversed in asingle smooth pass or throw to a target in a cerebral vessel without thestep-wise adjustment of their relative extensions and without relying onthe conventional step-wise advancement technique, as described abovewith conventional microcatheters. The catheter 200 having the catheteradvancement element 300 extending through it allows a user to advancethem in unison in the same relative position from the first bend of thesiphon through the second bend beyond the terminal cavernous carotidartery into the ACA and MCA. Importantly, the advancement of the twocomponents can be performed in a single smooth movement through bothbends without any change of hand position.

The catheter advancement element 300 can be in a juxtapositionedrelative to the catheter 200 that provides an optimum relative extensionbetween the two components for single smooth advancement. The catheteradvancement element 300 can be positioned through the lumen of thecatheter 200 such that its distal tip 346 extends beyond a distal end ofthe catheter 200. The distal tip 346 of the catheter advancement element300 eliminates the stepped transition between the inner member and theouter catheter 200 thereby avoiding issues with catching on branchingvessels within the region of the vasculature such that the catheter 200may easily traverse the multiple angulated turns of the carotid siphonCS. The optimum relative extension, for example, can be the distal tip346 of the elongate body 360 extending distal to a distal end of thecatheter 200 as described elsewhere herein. A length of the distal tip346 extending distal to the distal end can be between 0.5 cm and about 3cm. This juxtaposition can be a locked engagement with a mechanicalelement or simply by a user holding the two components together.

The components can be advanced together with a guidewire, over aguidewire pre-positioned, or without any guidewire at all. In someimplementations, the guidewire can be pre-assembled with the catheteradvancement element 300 and catheter 200 such that the guidewire extendsthrough a lumen of the catheter advancement element 300, which is loadedthrough a lumen of the catheter 200, all prior to insertion into thepatient. The pre-assembled components can be simultaneously insertedinto the sheath 400 and advanced together up through and past the turnsof the carotid siphon. The guidewire can be positioned within a portionof the lumen of the catheter advancement element 300, but not extenddistal to the distal opening from the lumen so that the distal-most endof the guidewire remains housed within the catheter advancement element300 for optional use in a step of the procedure. For example, thecatheter advancement element 300 having a guidewire parked within itslumen proximal to the distal opening can be used to deliver the catheter200 to a target location or near a target location. The guidewire can beadvanced distally while the catheter advancement element 300 andcatheter 200 remain in a fixed position until a distal end of theguidewire is advanced beyond the distal opening a distance. The catheteradvancement element 300 with or without the catheter 200 can then beadvanced over the guidewire that distance. The guidewire can then bewithdrawn inside the lumen of the catheter advancement element 300.

The optimum relative extension of the catheter 200 and catheteradvancement element 300 can be based additionally on the staggering ofmaterial transitions. FIG. 11 is a schematic illustrating approximatelocations of the material transitions in the catheter advancementelement 300 and the approximate locations of the material transitions inthe catheter 200. For example, the catheter advancement element 300 caninclude a proximal portion 366, which can be a hypotube that is barestainless steel or coated with one or more polymers. The proximalportion 366 transitions at a location 1101 a to a region having amaterial hardness of about 55 D that transitions at a location 1101 b toa region having a material hardness of about 35 D that transitions at alocation 1101 c to a region have a material hardness of 35 D. Similarly,the catheter 200 can include a proximal extension 230 that is astainless steel ribbon. The proximal extension 230 transitions at alocation 1103 a to a region having a hardness of 72 D that transitionsat a location 1103 b to a region having a hardness of 55 D thattransitions at a location 1103 c to a region having a material hardnessof about 40 D that transitions at a location 1103 d to a region having amaterial hardness of about 35 D that transitions at a location 1103 e toa region have a material hardness of 25 D that transitions at a location1103 f to a region having a material hardness of about 85 A thattransitions at a location 1103 g to a region having a material hardnessof about 80 A. A distal-most region of the catheter advancement element300 can be formed of Tecothane having a material hardness of about 62 A.The locations 1101 of the catheter advancement element 300 and thelocations 1103 of the catheter 200 can be staggered such that thelocations are off-set from one another. More or fewer materialtransitions may exist within the catheter advancement element andcatheter.

The catheter 200 and catheter advancement element 300 can bepre-assembled at the time of manufacturing such that an optimum lengthof the catheter advancement element 300 extends distal to the distal endof catheter 200 and/or the material transitions are staggered. Anoptimum length of extension can be such that the entire length of thetapered distal tip of the catheter advancement element 300 extendsoutside the distal end of the catheter 200 such that the uniform outerdiameter of the catheter advancement element 300 aligns substantiallywith the distal end of the catheter 200. This can result in the greatestouter diameter of the elongate body 360 aligned substantially with thedistal end of the catheter 200 such that it remains inside the lumen ofthe catheter 200 and only the tapered region of the distal tip 346extends distal to the lumen of the catheter 200. This relativearrangement provide the best arrangement for advancement throughtortuous vessels where a lip at the distal end of the system would posethe greatest difficulty. This optimal pre-assembled arrangement can bemaintained by a coupler configured to engage with both the proximalextension 230 of the catheter 200 and the proximal portion 366 of thecatheter advancement element 300. The coupler can be used during aprocedure as described elsewhere herein. Alternatively, the coupler canbe removed prior to a procedure.

FIG. 12 illustrates an implementation of a coupler 1201 configured to beremoved prior to a procedure. The coupler 1201 can be a temporarycoupler configured to engage the catheter 200 and catheter advancementelement 300 only at the time of manufacturing and/or during storage. Insome implementations, the coupler 1201 can be a disc having a layer ofadhesive material on one side. The coupler 1201 is configured to captureboth the proximal extension 230 of the catheter 200 and the proximalportion 366 of the catheter advancement element 300 and maintain theoptimal pre-assembled extension arrangement. The coupler 1201 can betorn away from the proximal extension 230 and the proximal portion 366with ease and without leaving any residue. The coupler 1201 can a discof plastic material, such as polyimide. The hemispheres of the disk aredesigned to fold over onto themselves until the adhesive side of eachhemisphere engages one another thereby trapping the hypotubes of theproximal extension 230 and proximal portion 366 of the catheter 200 andcatheter advancement element 300, respectively, therebetween along anequator of the disc. The disc can include a pair of notches 1203 nearthe equator such that the overall shape of the disc is bi-lobed. Thedisc can include a first rounded lobe 1202 a on one side of the pair ofnotches 1203 and a second rounded lobe 1202 b on the opposite side ofthe pair of notches 1203, each of the first and second lobe 1202 a, 1202b having matching shapes. The hypotubes can be captured along theequator of the disc between the first and second lobes 1202 a, 1202 bfolding over onto each other such that their adhesive sides can capturethe hypotubes. The apex of each notch 1203 aligns with the equator ofthe disc and each can include a cut or notch extension 1205 extendingtoward the center of the disc. The apex of each notch 1203 incoordination with the notch extensions 1205 aid in getting the tearstarted creating a stress concentration tear-away location when thecatheter system is ready to be used. The notch extensions 1205 help todirect the tear direction. The coupler 1201 is thereby engaged with boththe hypotube proximal extension 230 of the catheter 200 and the hypotubeproximal body 330 of the catheter advancement element 300, which isinserted through the lumen of the catheter 200. The coupled engagementallows the two components engaged with one another to be easily insertedinto the packaging hoop while maintaining the optimal relative extensionof the components. The coupler 1201 avoids catching on the packaginghoop due to the rounded, smooth surfaces and lack of edges to catch.Prior to use of the catheter system 100, a user can remove the catheter200/catheter advancement element 300 from the packaging hoop. Thecoupler 1201 can be torn away from the hypotubes by a user pulling onthe folded over lobes 1202 a, 1202 b adhered to one another. The entirecoupler 1201 is thereby removed from the hypotubes without leaving anyresidue on the hypotubes. The system is immediately ready for insertionat an optimal pre-assembled relative extension.

The dimensions of the coupler 1201 are such that they provide ampleengagement with the hypotubes thereby locking them together andmaintaining the relative extension yet not so large as to negativelyimpact storage within the packaging hoop. The disc of the coupler 1201can have a diameter that is about 0.75″ to about 1″. The disc can berelatively thin such as between about 0.0005″ to about 0.0015″ thickpolyimide. In some implementations, the polyimide disc is about 0.001″thick. One side of the discs can include a layer of adhesive, such assilicone adhesive. The adhesive can be about 0.0015″ thick. Each side ofthe notches 1203 can have a length 1 extending between the outerperimeter of the disc and the apex of the notch 1203. The length can beabout 0.200″ long. The sides can form an angle θ relative to one anotherthat is between about 50 and 70 degrees, preferably about 60 degrees.

The catheter and the catheter advancement element may be releaseably,pre-packaged in a locked position according to any of a variety ofmethods (e.g. shrink-wrap, and other known methods).

Materials

One or more components of the catheters described herein may include orbe made from a variety of materials including one or more of a metal,metal alloy, polymer, a metal-polymer composite, ceramics, hydrophilicpolymers, polyacrylamide, polyethers, polyamides, polyethylenes,polyurethanes, copolymers thereof, polyvinyl chloride (PVC), PEO,PEO-impregnated polyurethanes such as Hydrothane, Tecophilicpolyurethane, Tecothane, PEO soft segmented polyurethane blended withTecoflex, thermoplastic starch, PVP, and combinations thereof, and thelike, or other suitable materials.

Some examples of suitable metals and metal alloys include stainlesssteel, such as 304V, 304L, and 316LV stainless steel; mild steel;nickel-titanium alloy such as linear-elastic and/or super-elasticnitinol; other nickel alloys such as nickel-chromium-molybdenum alloys(e.g., UNS: N06625 such as INCONEL® 625, UNS: N06022 such as HASTELLOY®C-22®, UNS: N10276 such as HASTELLOY® C276®, other HASTELLOY® alloys,and the like), nickel-copper alloys (e.g., UNS: N04400 such as MONEL®400, NICKELVAC® 400, NICORROS® 400, and the like),nickel-cobalt-chromium-molybdenum alloys (e.g., UNS: R30035 such asMP35-N® and the like), nickel-molybdenum alloys (e.g., UNS: N10665 suchas HASTELLOY® ALLOY B2®), other nickel-chromium alloys, othernickel-molybdenum alloys, other nickel-cobalt alloys, other nickel-ironalloys, other nickel-copper alloys, other nickel-tungsten or tungstenalloys, and the like; cobalt-chromium alloys; cobalt-chromium-molybdenumalloys (e.g., UNS: R30003 such as ELGILOY®, PHYNOX®, and the like);platinum enriched stainless steel; titanium; combinations thereof; andthe like; or any other suitable material and as described elsewhereherein.

Inner liner materials of the catheters described herein can include lowfriction polymers such as PTFE (polytetrafluoroethylene) or FEP(fluorinated ethylene propylene), PTFE with polyurethane layer(Tecoflex). Reinforcement layer materials of the catheters describedherein can be incorporated to provide mechanical integrity for applyingtorque and/or to prevent flattening or kinking such as metals includingstainless steel, Nitinol, Nitinol braid, helical ribbon, helical wire,cut stainless steel, or the like, or stiff polymers such as PEEK.Reinforcement fiber materials of the catheters described herein caninclude various high tenacity polymers like Kevlar, polyester,meta-para-aramide, PEEK, single fiber, multi-fiber bundles, high tensilestrength polymers, metals, or alloys, and the like. Outer jacketmaterials of the catheters described herein can provide mechanicalintegrity and can be contracted of a variety of materials such aspolyethylene, polyurethane, PEBAX, nylon, Tecothane, and the like. Othercoating materials of the catheters described herein include paralene,Teflon, silicone, polyimide-polytetrafluoroetheylene, and the like.

Implementations describe catheters and delivery systems and methods todeliver catheters to target anatomies. However, while someimplementations are described with specific regard to deliveringcatheters to a target vessel of a neurovascular anatomy such as acerebral vessel, the implementations are not so limited and certainimplementations may also be applicable to other uses. For example, thecatheters can be adapted for delivery to different neuroanatomies, suchas subclavian, vertebral, carotid vessels as well as to the coronaryanatomy or peripheral vascular anatomy, to name only a few possibleapplications. It should also be appreciated that although the systemsdescribed herein are described as being useful for treating a particularcondition or pathology, that the condition or pathology being treatedmay vary and are not intended to be limiting. Use of the terms“embolus,” “embolic,” “emboli,” “thrombus,” “occlusion,” etc. thatrelate to a target for treatment using the devices described herein arenot intended to be limiting. The terms may be used interchangeably andcan include, but are not limited to a blood clot, air bubble, smallfatty deposit, or other object carried within the bloodstream to adistant site or formed at a location in a vessel. The terms may be usedinterchangeably herein to refer to something that can cause a partial orfull occlusion of blood flow through or within the vessel.

In various implementations, description is made with reference to thefigures. However, certain implementations may be practiced without oneor more of these specific details, or in combination with other knownmethods and configurations. In the description, numerous specificdetails are set forth, such as specific configurations, dimensions, andprocesses, in order to provide a thorough understanding of theimplementations. In other instances, well-known processes andmanufacturing techniques have not been described in particular detail inorder to not unnecessarily obscure the description. Reference throughoutthis specification to “one embodiment,” “an embodiment,” “oneimplementation, “an implementation,” or the like, means that aparticular feature, structure, configuration, or characteristicdescribed is included in at least one embodiment or implementation.Thus, the appearance of the phrase “one embodiment,” “an embodiment,”“one implementation, “an implementation,” or the like, in various placesthroughout this specification are not necessarily referring to the sameembodiment or implementation. Furthermore, the particular features,structures, configurations, or characteristics may be combined in anysuitable manner in one or more implementations.

The use of relative terms throughout the description may denote arelative position or direction. For example, “distal” may indicate afirst direction away from a reference point. Similarly, “proximal” mayindicate a location in a second direction opposite to the firstdirection. However, such terms are provided to establish relative framesof reference, and are not intended to limit the use or orientation ofthe catheters and/or delivery systems to a specific configurationdescribed in the various implementations.

The word “about” means a range of values including the specified value,which a person of ordinary skill in the art would consider reasonablysimilar to the specified value. In embodiments, about means within astandard deviation using measurements generally acceptable in the art.In embodiments, about means a range extending to +/−10% of the specifiedvalue. In embodiments, about includes the specified value.

While this specification contains many specifics, these should not beconstrued as limitations on the scope of what is claimed or of what maybe claimed, but rather as descriptions of features specific toparticular embodiments. Certain features that are described in thisspecification in the context of separate embodiments can also beimplemented in combination in a single embodiment. Conversely, variousfeatures that are described in the context of a single embodiment canalso be implemented in multiple embodiments separately or in anysuitable sub-combination. Moreover, although features may be describedabove as acting in certain combinations and even initially claimed assuch, one or more features from a claimed combination can in some casesbe excised from the combination, and the claimed combination may bedirected to a sub-combination or a variation of a sub-combination.Similarly, while operations are depicted in the drawings in a particularorder, this should not be understood as requiring that such operationsbe performed in the particular order shown or in sequential order, orthat all illustrated operations be performed, to achieve desirableresults. Only a few examples and implementations are disclosed.Variations, modifications and enhancements to the described examples andimplementations and other implementations may be made based on what isdisclosed.

In the descriptions above and in the claims, phrases such as “at leastone of” or “one or more of” may occur followed by a conjunctive list ofelements or features. The term “and/or” may also occur in a list of twoor more elements or features. Unless otherwise implicitly or explicitlycontradicted by the context in which it is used, such a phrase isintended to mean any of the listed elements or features individually orany of the recited elements or features in combination with any of theother recited elements or features. For example, the phrases “at leastone of A and B;” “one or more of A and B;” and “A and/or B” are eachintended to mean “A alone, B alone, or A and B together.” A similarinterpretation is also intended for lists including three or more items.For example, the phrases “at least one of A, B, and C;” “one or more ofA, B, and C;” and “A, B, and/or C” are each intended to mean “A alone, Balone, C alone, A and B together, A and C together, B and C together, orA and B and C together.”

Use of the term “based on,” above and in the claims is intended to mean,“based at least in part on,” such that an unrecited feature or elementis also permissible.

What is claimed is:
 1. An intravascular catheter advancement device foradvancing a catheter within the neurovasculature, the catheteradvancement device comprising: a flexible elongate body having aproximal end, a distal end, and a single lumen extending therebetween,the flexible elongate body comprising: a proximal segment, wherein theproximal segment comprises a hypotube coated with a polymer; anintermediate segment comprising an unreinforced polymer having adurometer of no more than 72 D; and a tip segment, wherein the tipsegment is formed of a polymer different from the intermediate segmentand has a durometer of no more than about 35 D and a length of at least5 cm, wherein the tip segment has a tapered portion that tapers distallyfrom a first outer diameter to a second outer diameter over a length ofbetween 1 and 3 cm, wherein the catheter advancement device has a lengthconfigured to extend from outside a patient's body, through a femoralartery, and to a petrous portion of an internal carotid artery and aninner diameter less than 0.024 inches to accommodate a guidewire.
 2. Thedevice of claim 1, wherein flexible elongate body is formed without atubular inner liner.
 3. The device of claim 2, wherein the unreinforcedpolymer of the flexible elongate body incorporates a lubriciousadditive.
 4. The device of claim 1, wherein a taper angle of the wall ofthe tapered portion relative to a center line of the tapered portion isbetween 0.9 to 1.6 degrees or 2 to 3 degrees.
 5. The device of claim 1,wherein the second outer diameter is about ½ of the first outerdiameter.
 6. The device of claim 1, wherein the second outer diameter isabout 40% of the first outer diameter.
 7. The device of claim 1, whereinthe second outer diameter is about 65% of the first outer diameter. 8.The device of claim 1, wherein the intermediate segment includes a firstsegment having a material hardness of no more than 55 D and a secondsegment located proximal to the first segment having a material hardnessof no more than 72 D.
 9. A system including the device of claim 1,further comprising a catheter having a lumen and a distal end, whereinan outer diameter of the flexible elongate body is sized to bepositioned coaxially within the catheter lumen such that the taperedportion of the tip segment extends distally beyond the distal end of thecatheter to aid in delivery of the catheter to an intracranial vessel.10. The device of claim 1, wherein the flexible elongate body has aninsert length that is at least about 49 cm.
 11. The device of claim 10,wherein the location allows for positioning the material transitionproximal to the brachiocephalic take-off in the aortic arch when thedistal end is positioned within the petrous portion of the internalcarotid artery.
 12. The device of claim 1, wherein a location of amaterial transition between the unreinforced polymer and the hypotube isat least about 49 cm from the distal end of the flexible elongate body.13. The device of claim 1, wherein the hypotube has an inner diameter ofabout 0.021″ and an outer diameter of about 0.027″.
 14. The device ofclaim 1, wherein the first outer diameter is about 0.062″ up to about0.080″.
 15. The device of claim 14, wherein the second outer diameter isabout 0.031″.
 16. The device of claim 1, wherein the tip segmentcomprises a first radiopaque marker and a second radiopaque marker. 17.The device of claim 16, wherein the first radiopaque marker ispositioned on the first outer diameter and identifies a border betweenthe first outer diameter and the tapered portion.
 18. The device ofclaim 17, wherein the second radiopaque marker is positioned on thesecond outer diameter.
 19. The device of claim 16, wherein the first andsecond radiopaque markers have different widths.
 20. The device of claim16, wherein the first and second radiopaque markers are extruded polymerloaded with a radiopaque material, the radiopaque material comprisingplatinum/iridium, tungsten, or tantalum.
 21. The device of claim 1,wherein the device is configured for insertion over the guidewire suchthat the guidewire extends through the single lumen from the proximalend to the distal end.
 22. The device of claim 1, wherein the proximalend has a proximal opening and the distal end has a distal opening, theproximal and distal openings sized to receive the guidewire.
 23. Thedevice of claim 1, further comprising a rapid exchange opening through awall of the catheter advancement device.
 24. The device of claim 1,wherein the hypotube is coated with a lubricious polymer.
 25. The deviceof claim 24, wherein the lubricious polymer is PTFE.
 26. The device ofclaim 1, wherein the hypotube comprises a circular, oval, or trapezoidalD shape in cross-section.
 27. The device of claim 1, wherein thehypotube comprises a skived hypotube of stainless steel.
 28. The deviceof claim 27, wherein the skived hypotube is coupled to a proximal hub.29. The device of claim 28, wherein the proximal hub comprises a luerthread and a luer taper inside of the hub.
 30. The device of claim 28,wherein the proximal hub prevents insertion of the proximal hub througha proximal RHV.